Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain.
Gao B, Duan Z, Xu W, Xiong S.
Department of Immunology, Institute for Immunobiology, Shanghai Medical College of Fudan University, People's Republic of China.
Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. CONCLUSION: These findings suggest that TRIM22, which exhibits anti-HBV activity by acting as a transcriptional suppressor, may play an important role in the clearance of HBV. 作者: hantavirus 时间: 2015-8-28 16:19
Rojjer发表于 2009-9-3 20:04 ：
IF：10.734
算是熊思东教授这几年来的一份大手笔！
查了一下相关资料，TRIM22分子在HIV的研究中相对集中，也首先在HIV'的研究中发现具有抗病毒潜能。
近年也是成为抗HIV药物开发的靶点。
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene.
The protein encoded by this gene is a member of the tripartite motif (TRIM) family.The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon.
TRIM22 is also a target gene of the tumor suppressor protein p53，TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase.
References:
^ a b c "Entrez Gene: TRIM22 tripartite motif-containing 22". http://www.ncbi.nlm.nih.gov/site ... TermToSearch=10346.
^ a b Tissot C, Mechti N (June 1995). "Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression". J. Biol. Chem. 270 (25): 14891–8. PMID 7797467. http://www.jbc.org/cgi/content/full/270/25/14891.
^ Gongora C, Tissot C, Cerdan C, Mechti N (November 2000). "The interferon-inducible Staf50 gene is downregulated during T cell costimulation by CD2 and CD28". J. Interferon Cytokine Res. 20 (11): 955–61. doi:10.1089/10799900050198390. PMID 11096452.
^ Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A (May 2001). "The tripartite motif family identifies cell compartments". EMBO J. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMID 11331580.
^ Obad S, Olofsson T, Mechti N, Gullberg U, Drott K (October 2007). "Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation". J. Interferon Cytokine Res. 27 (10): 857–64. doi:10.1089/jir.2006.0180. PMID 17970695. http://luur.lub.lu.se/luur?func=downloadFile&fileOId=548138.
^ Duan Z, Gao B, Xu W, Xiong S (September 2008). "Identification of TRIM22 as a RING finger E3 ubiquitin ligase". Biochem. Biophys. Res. Commun. 374 (3): 502–6. doi:10.1016/j.bbrc.2008.07.070. PMID 18656448.
^ Huthoff H, Towers GJ (December 2008). "Restriction of retroviral replication by APOBEC3G/F and TRIM5alpha". Trends Microbiol. 16 (12): 612–9. doi:10.1016/j.tim.2008.08.013. PMID 18976920.
^ "Researchers discover gene that blocks HIV". Medicine & Health / HIV & AIDS. PhysOrg.com. 2008-02-29. http://www.physorg.com/news123505489.html. Retrieved 2009-02-22.
^ Barr SD, Smiley JR, Bushman FD (February 2008). "The interferon response inhibits HIV particle production by induction of TRIM22". PLoS Pathog. 4 (2): e1000007. doi:10.1371/journal.ppat.1000007. PMID 18389079 作者: hantavirus 时间: 2015-8-28 16:22
giggle334 发表于 2009-9-3 21:08 ：熊思东教授牛人一个 前不久听过他在兰大做的学术报告 特别精彩 条理清晰 思维广阔 佩服佩服！！ 作者: hantavirus 时间: 2015-8-28 16:25
Rojjer发表于 2009-9-3 21:18 ：