肠炎沙门氏菌毒力蛋白与宿主细胞蛋白相互作用的筛选和功能研究
|
摘要
肠炎沙门氏菌(Salmonella enterica)是一种典型的革兰氏阴性致病菌。该菌主要引起畜禽的胃肠炎以及人类肠炎和食物中毒,严重威胁着人畜健康。肠炎沙门氏菌表达两个Ⅲ型分泌系统(type Ⅲ secretion systems,T3SS),由毒力岛1和毒力岛2(pathogenicity islands1and2, SPI-1and SPI-2)分别编码。细菌依赖T3SS将毒力蛋白运输至宿主细胞内发挥作用。通常认为,毒力岛1编码的毒力蛋白在细菌入侵的过程中起到作用,而毒力岛2编码的蛋白则负责促进细菌在细胞中的生存,复制以及免疫逃逸等的调节。目前已经鉴定出了30几个T3SS毒力蛋白,但是它们中的绝大多数其生理功能尚未知晓或了解很少。
为探讨T3SS两个毒力岛的分泌蛋白的潜在生物学功能,并分析它们是怎样帮助细菌从入侵上皮细胞到在细胞内生存、复制的,鉴定这些毒力蛋白与宿主细胞蛋白的相互作用关系成为了必不可少的途径。本文从以下两个方面对T3SS分泌的毒力蛋白与宿主细胞蛋白的相互作用进行了系统分析,分别是：
1.通过酵母双杂交技术严格系统地筛选20个T3SS毒力蛋白(SsPH2, Ssel、 SpiC、SseF、SseG、SlrP、SseJ、SopD2、SifB、SipC、SipB、SipA、SopD、SipD、 SptP、SopA、SopE2、SrfB、SrfA、SrfJ)与宿主细胞的相互作用蛋白,并最终得到了超过300对的阳性相互作用结果。我们对其中部分结果进行了免疫共沉淀验证并通过文献进行了初步的功能分类分析,并从蛋白质组学的角度构建了相互作用网络草图。这些蛋白功能分布广泛,涵盖了能量代谢、细胞骨架和细胞运动、物质运输以及细胞内多种信号通路的调节。结合文献,我们获得的大量数据为揭示细菌侵染细胞及之后的生物学功能和细菌对宿主细胞各种生物学通路系统的影响提供了理论基础和事实依据。
2.选取SPI-2的重要毒力蛋白SsPH2为研究对象,探讨其对宿主内源泛素通路的影响作用。SsPH2作为一个最近才知晓的细菌编码的E3泛素连接酶,通过影响宿主内源泛素通路来促进细菌在宿主内的生存、复制以及调节宿主免疫反应。我们系统地鉴定了酵母双杂交得到的SsPH2作用对象,并着重研究了SsPH2与细胞蛋白LM04的相互作用。我们首先分别用不同方式验证了二者于体内、体外的相互作用,并探讨了其作用区域。接着我们通过体内、体外实验证实了SsPH2可以催化LM04蛋白的泛素化修饰。后面的进一步研究阐释了SsPH2对LM04的表达调控作用,我们发现SsPH2在体内稳定表达具有提高LM04蛋白水平的作用,通过深入研究这种调控的分子机制,我们发现SsPH2增强LM04蛋白水平是通过其对LM04的泛素化修饰来实现的。SsPH2抑制了LM04在细胞中的降解途径,从而延长了LM04蛋臼的半衰期。考虑到LM04与白细胞介素6(IL-6)途径的重要关系,我们猜测这种依赖于细菌SsPH2的LM04蛋白水平调节作用很可能影响了宿主IL-6信号通路,并调节了由IL-6介导的Stat3转录活性,从而影响宿主的早期炎症反应。以上发现揭示了SsPH2作为细菌编码的E3泛素连接酶通过特异性识别并泛素化修饰宿主蛋白LM04来实现细菌对宿主细胞生理功能的调节作用。
综上所述,通过本课题的研究我们鉴定出了数量庞大的肠炎沙门氏菌T3SS毒力蛋白在宿主细胞中的相互作用对象,为后续的进一步功能分析打下了坚实的理论基础。此外我们着重研究了毒力蛋白SsPH2与宿主蛋白LM04的相互作用机制,并发现了SsPH2对LM04的泛素化修饰以及调节作用。我们的研究工作为肠炎沙门氏菌乃至整个革兰氏阴性菌界毒力蛋白与宿主蛋白相互关系的思考提供很多新的研究思路和方向。
Salmonella entehca encodes two distinct type III secretion systems (T3SS) essential for virulence, encoded by genes located in the Salmonella pathogenicity islands1and2(SPI-1and SPI-2), respectively. These systems mediate the translocation of effectors into the eukaryotic host cell, where they alter cell signaling and manipulate host cell functions. However, the precise role of most effectors remains unknown. To better understand the molecular mechanism of Salmonella effectors interaction with host proteins, we made the following two approaches:
1. Systematic yeast two-hybrid library screens for25Salmonella effectors (SsPH2^SseI、SpiC、seF、SseG、SlrP、SseJ、SopD2、SifB、SipC、ipB、SipA、SopD、 SipD、SptP、SopA、SopE2、SrfE、SrfA、SrfJ) were performed, partial of results were further confirmed by coimmunoprecipitation (Co-IP). This gave rise to321distinct protein-protein interactions. Together with literature-curated data, these results provide a comprehensive insight into the complexity of the host-bacteria protein interaction network involving in Salmonella invasion and introcellular replication, and a detailed pathway for these Salmonella effectors from gene to function is proposed.
2. Using a yeast two-hybrid screen, we identified the LIM domain family protein LM04as a mammalian binding partner of the Salmonella effector SsPH2. The interaction was confirmed by GST pull-down and Co-IP assays. Using deletion mutants of both SsPH2and LMO4. we determined the LRR domain of SsPH2and the LIM domain of LM04were critical for the interaction. We further demonstrated that SsPH2was able to mediate ubiquitination of LM04both in vivo and in vitro, and this addition of poly-ubiquitin chains was neither lysine-48-linked nor lysine-63-linked. Furthermore,29lysine,67lysine located within the LIM domain were the major ubiquitination sites of LM04. We also discovered that stable expression of SsPH2in293T cells enhanced LM04protein expression, and this increase of protein level also depended on the SsPH2-mediated ubiquitination of LM04. Considering LM04acts as a scaffold for stabilization of the gpl30complex, which is a common receptor subunit of interleukin-6(IL-6), Hypothesis is that stable expression of SsPH2in293T cells reveals a positive regulation in IL-6signaling and results in a significant increase of transcriptional activity of Stat3(signal transducers and activators of transcription3). Identification of the ubiquitination substrates has been a major approach to understand the functions of ubiquitin ligases. Our findings assign a functional role to the Salmonella effector SsPH2as a binding partner and an E3ubiquitin ligase for mammalian LMO4. Through our project, we found some new clues which may facilitate future characterization of Salmonella effectors functions and functional mechanisms.
为探讨T3SS两个毒力岛的分泌蛋白的潜在生物学功能,并分析它们是怎样帮助细菌从入侵上皮细胞到在细胞内生存、复制的,鉴定这些毒力蛋白与宿主细胞蛋白的相互作用关系成为了必不可少的途径。本文从以下两个方面对T3SS分泌的毒力蛋白与宿主细胞蛋白的相互作用进行了系统分析,分别是：
1.通过酵母双杂交技术严格系统地筛选20个T3SS毒力蛋白(SsPH2, Ssel、 SpiC、SseF、SseG、SlrP、SseJ、SopD2、SifB、SipC、SipB、SipA、SopD、SipD、 SptP、SopA、SopE2、SrfB、SrfA、SrfJ)与宿主细胞的相互作用蛋白,并最终得到了超过300对的阳性相互作用结果。我们对其中部分结果进行了免疫共沉淀验证并通过文献进行了初步的功能分类分析,并从蛋白质组学的角度构建了相互作用网络草图。这些蛋白功能分布广泛,涵盖了能量代谢、细胞骨架和细胞运动、物质运输以及细胞内多种信号通路的调节。结合文献,我们获得的大量数据为揭示细菌侵染细胞及之后的生物学功能和细菌对宿主细胞各种生物学通路系统的影响提供了理论基础和事实依据。
2.选取SPI-2的重要毒力蛋白SsPH2为研究对象,探讨其对宿主内源泛素通路的影响作用。SsPH2作为一个最近才知晓的细菌编码的E3泛素连接酶,通过影响宿主内源泛素通路来促进细菌在宿主内的生存、复制以及调节宿主免疫反应。我们系统地鉴定了酵母双杂交得到的SsPH2作用对象,并着重研究了SsPH2与细胞蛋白LM04的相互作用。我们首先分别用不同方式验证了二者于体内、体外的相互作用,并探讨了其作用区域。接着我们通过体内、体外实验证实了SsPH2可以催化LM04蛋白的泛素化修饰。后面的进一步研究阐释了SsPH2对LM04的表达调控作用,我们发现SsPH2在体内稳定表达具有提高LM04蛋白水平的作用,通过深入研究这种调控的分子机制,我们发现SsPH2增强LM04蛋白水平是通过其对LM04的泛素化修饰来实现的。SsPH2抑制了LM04在细胞中的降解途径,从而延长了LM04蛋臼的半衰期。考虑到LM04与白细胞介素6(IL-6)途径的重要关系,我们猜测这种依赖于细菌SsPH2的LM04蛋白水平调节作用很可能影响了宿主IL-6信号通路,并调节了由IL-6介导的Stat3转录活性,从而影响宿主的早期炎症反应。以上发现揭示了SsPH2作为细菌编码的E3泛素连接酶通过特异性识别并泛素化修饰宿主蛋白LM04来实现细菌对宿主细胞生理功能的调节作用。
综上所述,通过本课题的研究我们鉴定出了数量庞大的肠炎沙门氏菌T3SS毒力蛋白在宿主细胞中的相互作用对象,为后续的进一步功能分析打下了坚实的理论基础。此外我们着重研究了毒力蛋白SsPH2与宿主蛋白LM04的相互作用机制,并发现了SsPH2对LM04的泛素化修饰以及调节作用。我们的研究工作为肠炎沙门氏菌乃至整个革兰氏阴性菌界毒力蛋白与宿主蛋白相互关系的思考提供很多新的研究思路和方向。
Salmonella entehca encodes two distinct type III secretion systems (T3SS) essential for virulence, encoded by genes located in the Salmonella pathogenicity islands1and2(SPI-1and SPI-2), respectively. These systems mediate the translocation of effectors into the eukaryotic host cell, where they alter cell signaling and manipulate host cell functions. However, the precise role of most effectors remains unknown. To better understand the molecular mechanism of Salmonella effectors interaction with host proteins, we made the following two approaches:
1. Systematic yeast two-hybrid library screens for25Salmonella effectors (SsPH2^SseI、SpiC、seF、SseG、SlrP、SseJ、SopD2、SifB、SipC、ipB、SipA、SopD、 SipD、SptP、SopA、SopE2、SrfE、SrfA、SrfJ) were performed, partial of results were further confirmed by coimmunoprecipitation (Co-IP). This gave rise to321distinct protein-protein interactions. Together with literature-curated data, these results provide a comprehensive insight into the complexity of the host-bacteria protein interaction network involving in Salmonella invasion and introcellular replication, and a detailed pathway for these Salmonella effectors from gene to function is proposed.
2. Using a yeast two-hybrid screen, we identified the LIM domain family protein LM04as a mammalian binding partner of the Salmonella effector SsPH2. The interaction was confirmed by GST pull-down and Co-IP assays. Using deletion mutants of both SsPH2and LMO4. we determined the LRR domain of SsPH2and the LIM domain of LM04were critical for the interaction. We further demonstrated that SsPH2was able to mediate ubiquitination of LM04both in vivo and in vitro, and this addition of poly-ubiquitin chains was neither lysine-48-linked nor lysine-63-linked. Furthermore,29lysine,67lysine located within the LIM domain were the major ubiquitination sites of LM04. We also discovered that stable expression of SsPH2in293T cells enhanced LM04protein expression, and this increase of protein level also depended on the SsPH2-mediated ubiquitination of LM04. Considering LM04acts as a scaffold for stabilization of the gpl30complex, which is a common receptor subunit of interleukin-6(IL-6), Hypothesis is that stable expression of SsPH2in293T cells reveals a positive regulation in IL-6signaling and results in a significant increase of transcriptional activity of Stat3(signal transducers and activators of transcription3). Identification of the ubiquitination substrates has been a major approach to understand the functions of ubiquitin ligases. Our findings assign a functional role to the Salmonella effector SsPH2as a binding partner and an E3ubiquitin ligase for mammalian LMO4. Through our project, we found some new clues which may facilitate future characterization of Salmonella effectors functions and functional mechanisms.
引文
1. Acheson, D. W. and S. Luccioli (2004). "Microbial-gut interactions in health and disease. Mucosal immune responses." Best Pract Res Clin Gastroenterol 18(2): 387-404.
2. Akira, S., Y. Nishio, et al. (1994). "Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway." Cell 77(1):63-71.
3. Aronheim, A., E. Zandi, et al. (1997). "Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions." Mol Cell Biol 17(6): 3094-3102.
4. Bach, I. (2000). "The LIM domain:regulation by association. " Mech Dev 91 (1-2): 5-17.
5. Bakowski, M. A., V. Braun, et al. (2008). "Salmonella-containing vacuoles: directing traffic and nesting to grow." Traffic 9(12):2022-2031.
6. Bernal-Bayard, J., E. Cardenal-Munoz, et al. (2010). "The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. " J Biol Chem 285(21):16360-16368.
7. Bernal-Bayard, J. and F. Ramos-Morales (2009). "Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin." J Biol Chem 284(40):27587-27595.
8. Biet, F., C. Locht, et al. (2002). "Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens." J Mol Med (Berl) 80(3): 147-162.
9. Chang, J., J. Chen, et al. (2005). "Delineation and characterization of the actin nucleation and effector translocation activities of Salmonella SipC." Mol Microbiol 55(5):1379-1389.
10. Chowers, Y., L. Cahalon, et al. (2000). "Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha-and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells." J Immunol 165(6):2955-2961.
11. Clavijo, R. I., C. Loui, et al. (2006). "Identification of genes associated with survival of Salmonella enterica serovar Enteritidis in chicken egg albumen." Appl Environ Microbiol 72(2):1055-1064.
12. Cunliffe, R. N. (2003). "Alpha-defensins in the gastrointestinal tract." Mol Immunol 40(7):463-467.
13. Dawid, I. B., J. J. Breen, et al. (1998). "LIM domains:multiple roles as adapters and functional modifiers in protein interactions." Trends Genet 14(4):156-162.
14. de Andrade, D. R. and D. R. de Andrade Junior (2003). "Typhoid fever as cellular microbiological model." Rev Inst Med Trop Sao Paulo 45(4):185-191.
15. Deiwick, J., S. P. Salcedo, et al. (2006). "The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche." Infect Immun 74(12):6965-6972.
16. Diao, J., Y. Zhang, et al. (2008). "Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. " Nat Struct Mol Biol 15(1):65-70.
17. Didier, C., L. Broday, et al. (2003). "RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization." Molecular and Cellular Biology 23(15):5331-5345.
18. Drecktrah, D., S. Levine-Wilkinson, et al. (2008). "Dynamic behavior of Salmonella-induced membrane tubules in epithelial cells." Traffic 9(12): 2117-2129.
19. Dreher, D., M. Kok, et al. (2002). "Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells." J Leukoc Biol 72(4): 743-751.
20. Evdokimov, A. G., D. E. Anderson, et al. (2001). "Unusual molecular architecture of the Yersinia pestis cytotoxin YopM:a leucine-rich repeat protein with the shortest repeating unit." J Mol Biol 312(4):807-821.
21. Fardini, Y., K. Chettab, et al. (2007). "The YfgL lipoprotein is essential for type III secretion system expression and virulence of Salmonella enterica Serovar Enteritidis. " Infect Immun 75(1):358-370.
22. Pass, E. and E. A. Groisman (2009). "Control of Salmonella pathogenicity island-2 gene expression." Curr Opin Microbiol 12(2):199-204.
23. Fischer, P., U. Lehmann, et al. (2004). "The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling." Biochem J 378(Pt 2):449-460.
24. Freeman, J. A., M. E. Ohl, et al. (2003). "The Salmonella enterica Serovai Typhimurium Translocated Effectors Sse.I and SifB Are Targeted to th Salmonella-Containing Vacuole. " Infection and Immunity 71(1):418-427.
25. Gabriel, P., I. Cakman, et al. (2002). "Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. " Exp Gerontol 37(2-3): 235-247.
26. Galan, J. E. and H. Wolf-Watz (2006). "Protein delivery into eukaryotic cells by type III secretion machines. " Nature 444(7119):567-573.
27. Giot, L., J. S. Bader, et al. (2003). "A protein interaction map of Drosophila melanogaster. " Science 302(5651):1727-1736.
28. Gong, H., G. P. Vu, et al. (2011). "A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors." PLoS Pathog 7(9):e1002120.
29. Grutz, G., A. Forster, et al. (1998). "Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1:a candidate for displacement by LMO proteins in T cell acute leukaemia." Oncogene 17(21): 2799-2803.
30. Habelhah, H., S. Takahashi, et al. (2004). "Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB. " EMBO J 23(2): 322-332.
31. Hanisch, J., J. Ehinger, et al. (2010). "Molecular dissection of Salmonella-induced membrane ruffling versus invasion." Cell Microbiol 12(1):84-98.
32. Heinrich, P. C., I. Behrmann, et al. (2003). "Principles of interleukin (IL)-6-type cytokine signalling and its regulation." Biochem J 374(Pt 1):1-20.
33. Heusipp, G., K. Spekker, et al. (2006). "YopM of Yersinia enterocolitica specifically interacts with alphal-antitrypsin without affecting the anti-protease activity." Microbiology 152(Pt 5):1327-1335.
34. Hibi, M. and T. Hirano (1998). "Signal transduction through cytokine receptors.' Int Rev Immunol 17(1-4):75-102.
35. Hibi, M., K. Nakajima, et al. (1996). "IL-6 cytokine family and signal transduction: a model of the cytokine system." J Mol Med (Berl) 74(1):1-12.
36. Hicks, S. W., G. Charron, et al. (2011). "Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. " Cell Host Microbe 10(1): 9-20.
37. Higashide, W., S. Dai, et al. (2002). "Involvement of SipA in modulating actii dynamics during Salmonella invasion into cultured epithelial cells." Cell Microbiol 4(6):357-365.
38. Hoeller, D. and I. Dikic (2009). "Targeting the ubiquitin system in cancer therapy. " Nature 458(7237):438-444.
39. Ihle, J. N. (2001). "The Stat family in cytokine signaling." Curr Opin Cell Biol 13(2):211-217.
40. Jacqueline F, B., et al. (1999). Stat3 as an Oncogene. Cell:295-303.
41. Jarvelainen, H. A., A. Galmiche, et al. (2003). "Caspase-1 activation by Salmonella." Trends Cell Biol 13(4):204-209.
42. Jepson, M. A. and M. A. Clark (2001). "The role of M cells in Salmonella infection. " Microbes Infect 3(14-15):1183-1190.
43. Jones-Carson, J., B. D. McCollister, et al. (2007). "Systemic CD8 T-cell memory response to a Salmonella pathogenicity island 2 effector is restricted to Salmonella enterica encountered in the gastrointestinal mucosa. " Infect Immun 75(6):2708-2716.
44. Jurata, L. W. and G. N. Gill (1998). "Structure and funct ion of LIM domains. " Curr Top Microbiol Immunol 228:75-113.
45. Kang, H., C. Loui, et al. (2006). "Survival characteristics of Salmonella enterica serovar Enteritidis in chicken egg albumen." Epidemiol Infect 134(5):967-976.
46. Kaur, T. and N. K. Ganguly (2003). "Modulation of gut physiology through enteric toxins." Mol Cell Biochem 253(1-2):15-19.
47. Kavsak, P., R. K. Rasmussen, et al. (2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. " Mol Cell 6(6): 1365-1375.
48. Kenny, D. A., L. W. Jurata, et al. (1998). "Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. " Proc Xatl Acad Sci U S A 95(19):11257-11262.
49. Kubori, T. and J. E. Galan (2003). "Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation." Cell 115(3): 333-342.
50. Kudryavtseva, E. I., T. M. Sugihara, et al. (2003). "Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a nove1 mammalian Grainyhead-like factor." Dev Dyn 226(4):604-617.
51. Layton, A. N. and E. E. Galyov (2007). "Salmonella-induced enteritis:molecular pathogenesis and therapeutic implications." Expert Rev Mol Med 9(18):1-17.
52. Lehmann, U., J. Schmitz, et al. (2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gpl30." J Biol Chem 278(1):661-671.
53. Li, J. J. and I. Herskowitz (1993). "Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. " Science 262(5141):1870-1874.
54. Lu, S. (2002). "The Global Regulator ArcA Controls Resistance to Reactive Nitrogen and Oxygen Intermediates in Salmonella enterica Serovar Enteritidis." Infection and Immunity 70(2):451-461.
55. Lu, S. (2002). "The Global Regulator ArcA Controls Resistance to Reactive Nitrogen and Oxygen Intermediates in Salmonella enterica Serovar Enteritidis. " Infect Immun 70(2):451-461.
56. Lu, S., P. B. Killoran, et al. (2003). "Association of Salmonella enterica Serovar Enteritidis YafD with Resistance to Chicken Egg Albumen. " Infection and Immunity 71(12):6734-6741.
57. Lufei, C., J. Ma, et al. (2003). "GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction." EMBO J 22(6):1325-1335.
58. Ly, K. T. and J. E. Casanova (2007). "Mechanisms of Salmonella entry into host cells." Cell Microbiol 9(9):2103-2111.
59. Mallo, G. V., M. Espina, et al. (2008). "SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34. " J Cell Biol 182(4):741-752.
60. Manetopoulos, C., A. Hansson, et al. (2003). "The LIM-only protein LMO4 modulates the transcriptional activity of HEN1. " Biochem Biophys Res Commun 307(4):891-899.
61. McGhie, E. J., R. D. Hayward, et al. (2001). "Cooperation between actin-binding proteins of invasive Salmonella:SipA potentiates SipC nucleation and bundling of actin." EMBO J 20(9):2131-2139.
62. Miao, E. A., M. Brittnacher, et al. (2003). "Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton." Mol Microbiol 48(2):401-415.
63. Novotny-Diermayr, V., B. Lin, et al. (2005). "Modulation of the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling by LM04 interaction. J Biol Chem 280(13):12747-12757.
64. Patel, J. C., K. Hueffer, et al. (2009). "Diversification of a Salmonel la virulence protein function by ubiquitin-dependent differential localization." Cell 137(2): 283-294.
65. Prieto, A. I., S. B. Hernandez, et al. (2009). "Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells." J Bacteriol 191(11):3615-3622.
66. Prouty, A. M., I. E. Brodsky, et al. (2004). "Transcriptional regulation of Salmonella enterica serovar Typhimurium genes by bile. " FEMS Immunol Med Microbiol 41(2):177-185.
67. Quezada, C. M., S. W. Hicks, et al. (2009). "A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. " Proc Natl Acad Sci USA 106(12):4864-4869.
68. Rabbitts, T. H. (1994). "Chromosomal translocations in human cancer." Nature 372(6502):143-149.
69. Racevskis, J., A. Dill, et al. (1999). "Molecular cloning of LMO41, a new human LIM domain gene." Biochim Biophys Acta 1445(1):148-153.
70. Rajashekar, R., D. Liebl, et al. (2008). "Dynamic remodeling of the endosomal system during formation of Salmonella-induced filaments by intracellular Salmonella enterica." Traffic 9(12):2100-2116.
71. Ramsden, A. E., L. J. Mota, et al. (2007). "The SPI-2 type Ⅲ secretion system restricts motility of Salmonella-containing vacuoles." Cell Microbiol 9(10): 2517-2529.
72. Rescigno, M., G. Rotta, et al. (2001). "Dendritic cells shuttle microbes across gut epithelial monolayers." Immunobiology 204(5):572-581.
73. Revolledo, L., C. S. Ferreira, et al. (2009). "Prevention of Salmonella Typhimurium colonization and organ invasion by combination treatment in broiler chicks. " Poult Sci 88(4):734-743.
74. Rohde, J. R., A. Breitkreutz, et al. (2007). "Type Ⅲ secretion effectors of the IpaH family are E3 ubiquitin ligases." Cell Host Microbe 1(1):77-83.
75. Sampathkumar, B., G. G. Khachatourians, et al. (2004). "Treatment of Salmonel la enterica serovar Enteritidis with a sublethal concentration of trisodium phosphati or alkaline pH induces thermotolerance. " Appl Environ Microbiol 70(8):4613-4620.
76. Sanchez-Garcia, I. and T. H. Rabbitts (1994). "The LIM domain:a new structural motif found in zinc-finger-like proteins." Trends Genet 10(9):315-320.
77. Schaper, F., C. Gendo, et al. (1998). "Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jakl and limits acute-phase protein expression." Biochem J 335 (Pt 3):557-565.
78. Schwan, W. R., X. Z. Huang, et al. (2000). "Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages. " Infect Immun 68(3):1005-1013.
79. Sigismund, S., T. Woelk, et al. (2005). "Clathrin-independent endocytosis of ubiquitinated cargos. " Proc Natl Acad Sci U S A 102(8):2760-2765.
80. Sugihara, T. M., I. Bach, et al. (1998). "Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. " Proc Natl Acad Sci U S A 95(26):15418-15423.
81. Sum, E. Y., B. Peng, et al. (2002). "The LIM domain protein LM04 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity. " J Biol Chem 277(10):7849-7856.
82. Szeto, J., A. Namolovan, et al. (2009). "Salmonella-containing vacuoles display centrifugal movement associated with cell-to-cell transfer in epithelial cells." Infect Immun 77(3):996-1007.
83. Terebiznik, M. R.,0. V. Vieira, et al. (2002). "Elimination of host cell Ptdlns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella." Nat Cell Biol 4(10):766-773.
84. Thomas, M., J. M. Boname, et al. (2008). "Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity. " Proc Natl Acad Sci U S A 105(5):1656-1661.
85. Thomas, M. and D. W. Holden (2009). "Ubiquitination-a bacterial effector's ticket to ride." Cell Host Microbe 5(4):309-311.
86. Tian, Y., N. Wang, et al. (2010). "Repression of Lim only protein 4-activated transcription inhibits proliferation and induces apoptosis of normal mammary epithelial cells and breast cancer cells." Clin Exp Metastasis 27(7):455-463.
87. Vidal, M., R. K. Brachmann, et al. (1996). "Reverse two-hybrid and one-hybri(?) systems to detect dissociation of protein-protein and DNA-protein interactions.' Proc Natl Acad Sci U S A 93(19):10315-10320.
88. Vila, B., A. Fontgibell, et al. (2009). "Reduction of Salmonella enterica var. Enteritidis colonization and invasion by Bacillus cereus var. toyoi inclusion in poultry feeds." Poult Sci 88(5):975-979.
89. Yang, M., Z. Wu, et al. (1995). "Protein-peptide interactions analyzed with the yeast two-hybrid system." Nucleic Acids Res 23(7):1152-1156.
90. YANG, S. (2002). "Changes in Three Type of Ubiquitin mRNA and Ubiquitin-protein Conjugate Levels During Lens Development.
91. Yao, Q., J. Cui, et al. (2009). "A bacterial type Ⅲ effector family uses the papain-like hydrolytic activity to arrest the host cell cycle. " Proc Natl Acad Sci USA 106(10):3716-3721.
92. Zhang, B., B. Kraemer, et al. (1999). "Yeast three-hybrid system to detect and analyze interactions between RNA and protein." Methods Enzymol 306:93-113.
93. Zhang, Y., W. Higashide, et al. (2005). "Recognition and ubiquitination of Salmonella type Ⅲ effector SopA by a ubiquitin E3 ligase, HsRMAl." J Biol Chem 280(46):38682-38688.
94. Zhong, B., L. Zhang, et al. (2009). "The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA." Immunity 30(3): 397-407.
95. Zhong, B., Y. Zhang, et al. (2010). "The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation." J Immunol 184(11):6249-6255.
96. Zhou, X., N. Mantis, et al. (2000). "Salmonella typhimurium induces apoptosis in human monocyte-derived macrophages. " Microbiol Immunol 44(12):987-995.
97.孙佳,等.(2003)。“LIM蛋白家族的研究进展。”生理科学进展2003年第34卷第2期.
98.齐义鹏.(1999).“基因及其操作原理”.武汉大学出版社.
99.孙乃恩,孙东旭,朱德熙.(1990).“分子遗传学”.南京大学出版社.
100.黄培堂等译.(2005).”分子克隆实验指南(第三版).”科学出版社.
2. Akira, S., Y. Nishio, et al. (1994). "Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway." Cell 77(1):63-71.
3. Aronheim, A., E. Zandi, et al. (1997). "Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions." Mol Cell Biol 17(6): 3094-3102.
4. Bach, I. (2000). "The LIM domain:regulation by association. " Mech Dev 91 (1-2): 5-17.
5. Bakowski, M. A., V. Braun, et al. (2008). "Salmonella-containing vacuoles: directing traffic and nesting to grow." Traffic 9(12):2022-2031.
6. Bernal-Bayard, J., E. Cardenal-Munoz, et al. (2010). "The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. " J Biol Chem 285(21):16360-16368.
7. Bernal-Bayard, J. and F. Ramos-Morales (2009). "Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin." J Biol Chem 284(40):27587-27595.
8. Biet, F., C. Locht, et al. (2002). "Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens." J Mol Med (Berl) 80(3): 147-162.
9. Chang, J., J. Chen, et al. (2005). "Delineation and characterization of the actin nucleation and effector translocation activities of Salmonella SipC." Mol Microbiol 55(5):1379-1389.
10. Chowers, Y., L. Cahalon, et al. (2000). "Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha-and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells." J Immunol 165(6):2955-2961.
11. Clavijo, R. I., C. Loui, et al. (2006). "Identification of genes associated with survival of Salmonella enterica serovar Enteritidis in chicken egg albumen." Appl Environ Microbiol 72(2):1055-1064.
12. Cunliffe, R. N. (2003). "Alpha-defensins in the gastrointestinal tract." Mol Immunol 40(7):463-467.
13. Dawid, I. B., J. J. Breen, et al. (1998). "LIM domains:multiple roles as adapters and functional modifiers in protein interactions." Trends Genet 14(4):156-162.
14. de Andrade, D. R. and D. R. de Andrade Junior (2003). "Typhoid fever as cellular microbiological model." Rev Inst Med Trop Sao Paulo 45(4):185-191.
15. Deiwick, J., S. P. Salcedo, et al. (2006). "The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche." Infect Immun 74(12):6965-6972.
16. Diao, J., Y. Zhang, et al. (2008). "Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. " Nat Struct Mol Biol 15(1):65-70.
17. Didier, C., L. Broday, et al. (2003). "RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization." Molecular and Cellular Biology 23(15):5331-5345.
18. Drecktrah, D., S. Levine-Wilkinson, et al. (2008). "Dynamic behavior of Salmonella-induced membrane tubules in epithelial cells." Traffic 9(12): 2117-2129.
19. Dreher, D., M. Kok, et al. (2002). "Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells." J Leukoc Biol 72(4): 743-751.
20. Evdokimov, A. G., D. E. Anderson, et al. (2001). "Unusual molecular architecture of the Yersinia pestis cytotoxin YopM:a leucine-rich repeat protein with the shortest repeating unit." J Mol Biol 312(4):807-821.
21. Fardini, Y., K. Chettab, et al. (2007). "The YfgL lipoprotein is essential for type III secretion system expression and virulence of Salmonella enterica Serovar Enteritidis. " Infect Immun 75(1):358-370.
22. Pass, E. and E. A. Groisman (2009). "Control of Salmonella pathogenicity island-2 gene expression." Curr Opin Microbiol 12(2):199-204.
23. Fischer, P., U. Lehmann, et al. (2004). "The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling." Biochem J 378(Pt 2):449-460.
24. Freeman, J. A., M. E. Ohl, et al. (2003). "The Salmonella enterica Serovai Typhimurium Translocated Effectors Sse.I and SifB Are Targeted to th Salmonella-Containing Vacuole. " Infection and Immunity 71(1):418-427.
25. Gabriel, P., I. Cakman, et al. (2002). "Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. " Exp Gerontol 37(2-3): 235-247.
26. Galan, J. E. and H. Wolf-Watz (2006). "Protein delivery into eukaryotic cells by type III secretion machines. " Nature 444(7119):567-573.
27. Giot, L., J. S. Bader, et al. (2003). "A protein interaction map of Drosophila melanogaster. " Science 302(5651):1727-1736.
28. Gong, H., G. P. Vu, et al. (2011). "A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors." PLoS Pathog 7(9):e1002120.
29. Grutz, G., A. Forster, et al. (1998). "Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1:a candidate for displacement by LMO proteins in T cell acute leukaemia." Oncogene 17(21): 2799-2803.
30. Habelhah, H., S. Takahashi, et al. (2004). "Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB. " EMBO J 23(2): 322-332.
31. Hanisch, J., J. Ehinger, et al. (2010). "Molecular dissection of Salmonella-induced membrane ruffling versus invasion." Cell Microbiol 12(1):84-98.
32. Heinrich, P. C., I. Behrmann, et al. (2003). "Principles of interleukin (IL)-6-type cytokine signalling and its regulation." Biochem J 374(Pt 1):1-20.
33. Heusipp, G., K. Spekker, et al. (2006). "YopM of Yersinia enterocolitica specifically interacts with alphal-antitrypsin without affecting the anti-protease activity." Microbiology 152(Pt 5):1327-1335.
34. Hibi, M. and T. Hirano (1998). "Signal transduction through cytokine receptors.' Int Rev Immunol 17(1-4):75-102.
35. Hibi, M., K. Nakajima, et al. (1996). "IL-6 cytokine family and signal transduction: a model of the cytokine system." J Mol Med (Berl) 74(1):1-12.
36. Hicks, S. W., G. Charron, et al. (2011). "Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. " Cell Host Microbe 10(1): 9-20.
37. Higashide, W., S. Dai, et al. (2002). "Involvement of SipA in modulating actii dynamics during Salmonella invasion into cultured epithelial cells." Cell Microbiol 4(6):357-365.
38. Hoeller, D. and I. Dikic (2009). "Targeting the ubiquitin system in cancer therapy. " Nature 458(7237):438-444.
39. Ihle, J. N. (2001). "The Stat family in cytokine signaling." Curr Opin Cell Biol 13(2):211-217.
40. Jacqueline F, B., et al. (1999). Stat3 as an Oncogene. Cell:295-303.
41. Jarvelainen, H. A., A. Galmiche, et al. (2003). "Caspase-1 activation by Salmonella." Trends Cell Biol 13(4):204-209.
42. Jepson, M. A. and M. A. Clark (2001). "The role of M cells in Salmonella infection. " Microbes Infect 3(14-15):1183-1190.
43. Jones-Carson, J., B. D. McCollister, et al. (2007). "Systemic CD8 T-cell memory response to a Salmonella pathogenicity island 2 effector is restricted to Salmonella enterica encountered in the gastrointestinal mucosa. " Infect Immun 75(6):2708-2716.
44. Jurata, L. W. and G. N. Gill (1998). "Structure and funct ion of LIM domains. " Curr Top Microbiol Immunol 228:75-113.
45. Kang, H., C. Loui, et al. (2006). "Survival characteristics of Salmonella enterica serovar Enteritidis in chicken egg albumen." Epidemiol Infect 134(5):967-976.
46. Kaur, T. and N. K. Ganguly (2003). "Modulation of gut physiology through enteric toxins." Mol Cell Biochem 253(1-2):15-19.
47. Kavsak, P., R. K. Rasmussen, et al. (2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. " Mol Cell 6(6): 1365-1375.
48. Kenny, D. A., L. W. Jurata, et al. (1998). "Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. " Proc Xatl Acad Sci U S A 95(19):11257-11262.
49. Kubori, T. and J. E. Galan (2003). "Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation." Cell 115(3): 333-342.
50. Kudryavtseva, E. I., T. M. Sugihara, et al. (2003). "Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a nove1 mammalian Grainyhead-like factor." Dev Dyn 226(4):604-617.
51. Layton, A. N. and E. E. Galyov (2007). "Salmonella-induced enteritis:molecular pathogenesis and therapeutic implications." Expert Rev Mol Med 9(18):1-17.
52. Lehmann, U., J. Schmitz, et al. (2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gpl30." J Biol Chem 278(1):661-671.
53. Li, J. J. and I. Herskowitz (1993). "Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. " Science 262(5141):1870-1874.
54. Lu, S. (2002). "The Global Regulator ArcA Controls Resistance to Reactive Nitrogen and Oxygen Intermediates in Salmonella enterica Serovar Enteritidis." Infection and Immunity 70(2):451-461.
55. Lu, S. (2002). "The Global Regulator ArcA Controls Resistance to Reactive Nitrogen and Oxygen Intermediates in Salmonella enterica Serovar Enteritidis. " Infect Immun 70(2):451-461.
56. Lu, S., P. B. Killoran, et al. (2003). "Association of Salmonella enterica Serovar Enteritidis YafD with Resistance to Chicken Egg Albumen. " Infection and Immunity 71(12):6734-6741.
57. Lufei, C., J. Ma, et al. (2003). "GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction." EMBO J 22(6):1325-1335.
58. Ly, K. T. and J. E. Casanova (2007). "Mechanisms of Salmonella entry into host cells." Cell Microbiol 9(9):2103-2111.
59. Mallo, G. V., M. Espina, et al. (2008). "SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34. " J Cell Biol 182(4):741-752.
60. Manetopoulos, C., A. Hansson, et al. (2003). "The LIM-only protein LMO4 modulates the transcriptional activity of HEN1. " Biochem Biophys Res Commun 307(4):891-899.
61. McGhie, E. J., R. D. Hayward, et al. (2001). "Cooperation between actin-binding proteins of invasive Salmonella:SipA potentiates SipC nucleation and bundling of actin." EMBO J 20(9):2131-2139.
62. Miao, E. A., M. Brittnacher, et al. (2003). "Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton." Mol Microbiol 48(2):401-415.
63. Novotny-Diermayr, V., B. Lin, et al. (2005). "Modulation of the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling by LM04 interaction. J Biol Chem 280(13):12747-12757.
64. Patel, J. C., K. Hueffer, et al. (2009). "Diversification of a Salmonel la virulence protein function by ubiquitin-dependent differential localization." Cell 137(2): 283-294.
65. Prieto, A. I., S. B. Hernandez, et al. (2009). "Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells." J Bacteriol 191(11):3615-3622.
66. Prouty, A. M., I. E. Brodsky, et al. (2004). "Transcriptional regulation of Salmonella enterica serovar Typhimurium genes by bile. " FEMS Immunol Med Microbiol 41(2):177-185.
67. Quezada, C. M., S. W. Hicks, et al. (2009). "A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. " Proc Natl Acad Sci USA 106(12):4864-4869.
68. Rabbitts, T. H. (1994). "Chromosomal translocations in human cancer." Nature 372(6502):143-149.
69. Racevskis, J., A. Dill, et al. (1999). "Molecular cloning of LMO41, a new human LIM domain gene." Biochim Biophys Acta 1445(1):148-153.
70. Rajashekar, R., D. Liebl, et al. (2008). "Dynamic remodeling of the endosomal system during formation of Salmonella-induced filaments by intracellular Salmonella enterica." Traffic 9(12):2100-2116.
71. Ramsden, A. E., L. J. Mota, et al. (2007). "The SPI-2 type Ⅲ secretion system restricts motility of Salmonella-containing vacuoles." Cell Microbiol 9(10): 2517-2529.
72. Rescigno, M., G. Rotta, et al. (2001). "Dendritic cells shuttle microbes across gut epithelial monolayers." Immunobiology 204(5):572-581.
73. Revolledo, L., C. S. Ferreira, et al. (2009). "Prevention of Salmonella Typhimurium colonization and organ invasion by combination treatment in broiler chicks. " Poult Sci 88(4):734-743.
74. Rohde, J. R., A. Breitkreutz, et al. (2007). "Type Ⅲ secretion effectors of the IpaH family are E3 ubiquitin ligases." Cell Host Microbe 1(1):77-83.
75. Sampathkumar, B., G. G. Khachatourians, et al. (2004). "Treatment of Salmonel la enterica serovar Enteritidis with a sublethal concentration of trisodium phosphati or alkaline pH induces thermotolerance. " Appl Environ Microbiol 70(8):4613-4620.
76. Sanchez-Garcia, I. and T. H. Rabbitts (1994). "The LIM domain:a new structural motif found in zinc-finger-like proteins." Trends Genet 10(9):315-320.
77. Schaper, F., C. Gendo, et al. (1998). "Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jakl and limits acute-phase protein expression." Biochem J 335 (Pt 3):557-565.
78. Schwan, W. R., X. Z. Huang, et al. (2000). "Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages. " Infect Immun 68(3):1005-1013.
79. Sigismund, S., T. Woelk, et al. (2005). "Clathrin-independent endocytosis of ubiquitinated cargos. " Proc Natl Acad Sci U S A 102(8):2760-2765.
80. Sugihara, T. M., I. Bach, et al. (1998). "Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. " Proc Natl Acad Sci U S A 95(26):15418-15423.
81. Sum, E. Y., B. Peng, et al. (2002). "The LIM domain protein LM04 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity. " J Biol Chem 277(10):7849-7856.
82. Szeto, J., A. Namolovan, et al. (2009). "Salmonella-containing vacuoles display centrifugal movement associated with cell-to-cell transfer in epithelial cells." Infect Immun 77(3):996-1007.
83. Terebiznik, M. R.,0. V. Vieira, et al. (2002). "Elimination of host cell Ptdlns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella." Nat Cell Biol 4(10):766-773.
84. Thomas, M., J. M. Boname, et al. (2008). "Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity. " Proc Natl Acad Sci U S A 105(5):1656-1661.
85. Thomas, M. and D. W. Holden (2009). "Ubiquitination-a bacterial effector's ticket to ride." Cell Host Microbe 5(4):309-311.
86. Tian, Y., N. Wang, et al. (2010). "Repression of Lim only protein 4-activated transcription inhibits proliferation and induces apoptosis of normal mammary epithelial cells and breast cancer cells." Clin Exp Metastasis 27(7):455-463.
87. Vidal, M., R. K. Brachmann, et al. (1996). "Reverse two-hybrid and one-hybri(?) systems to detect dissociation of protein-protein and DNA-protein interactions.' Proc Natl Acad Sci U S A 93(19):10315-10320.
88. Vila, B., A. Fontgibell, et al. (2009). "Reduction of Salmonella enterica var. Enteritidis colonization and invasion by Bacillus cereus var. toyoi inclusion in poultry feeds." Poult Sci 88(5):975-979.
89. Yang, M., Z. Wu, et al. (1995). "Protein-peptide interactions analyzed with the yeast two-hybrid system." Nucleic Acids Res 23(7):1152-1156.
90. YANG, S. (2002). "Changes in Three Type of Ubiquitin mRNA and Ubiquitin-protein Conjugate Levels During Lens Development.
91. Yao, Q., J. Cui, et al. (2009). "A bacterial type Ⅲ effector family uses the papain-like hydrolytic activity to arrest the host cell cycle. " Proc Natl Acad Sci USA 106(10):3716-3721.
92. Zhang, B., B. Kraemer, et al. (1999). "Yeast three-hybrid system to detect and analyze interactions between RNA and protein." Methods Enzymol 306:93-113.
93. Zhang, Y., W. Higashide, et al. (2005). "Recognition and ubiquitination of Salmonella type Ⅲ effector SopA by a ubiquitin E3 ligase, HsRMAl." J Biol Chem 280(46):38682-38688.
94. Zhong, B., L. Zhang, et al. (2009). "The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA." Immunity 30(3): 397-407.
95. Zhong, B., Y. Zhang, et al. (2010). "The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation." J Immunol 184(11):6249-6255.
96. Zhou, X., N. Mantis, et al. (2000). "Salmonella typhimurium induces apoptosis in human monocyte-derived macrophages. " Microbiol Immunol 44(12):987-995.
97.孙佳,等.(2003)。“LIM蛋白家族的研究进展。”生理科学进展2003年第34卷第2期.
98.齐义鹏.(1999).“基因及其操作原理”.武汉大学出版社.
99.孙乃恩,孙东旭,朱德熙.(1990).“分子遗传学”.南京大学出版社.
100.黄培堂等译.(2005).”分子克隆实验指南(第三版).”科学出版社.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |