“TSG101”的意思、由来-开放百科全书

Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.

Function

The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.^[1]

The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions.^[2]^[3]

HIV

TSG101 seems to play an important role in the pathogenesis of HIV. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB),^[4] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.^[5]

Interactions

Orthologue, Vps23

In humans, the orthologue of vps23 which has a component of ESCRT-1 is called Tsg101. Mutations in Tsg-101 have been linked to cervical, breast, prostate and gastrointestinal cancers. In molecular biology, vps23 (vacuolar protein sorting) is a protein domain. Vps proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. More specifically, vps23 is a component of ESCRT-I. The ESCRT complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis and budding of HIV.

Structure

Yeast ESCRT-I consists of three protein subunits, VPS23, VPS28, and VPS37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues.

See also

References

1. ^{{cite web | title = Entrez Gene: TSG101 tumor susceptibility gene 101| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7251| accessdate = }}
2. ^{{cite journal | vauthors = Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB, Vallis Y, Emr SD, Williams RL | title = ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes | journal = Cell | volume = 125 | issue = 1 | pages = 99–111 | date = April 2006 | pmid = 16615893 | doi = 10.1016/j.cell.2006.01.047 | url = }}
3. ^{{cite journal | vauthors = Kostelansky MS, Sun J, Lee S, Kim J, Ghirlando R, Hierro A, Emr SD, Hurley JH | title = Structural and functional organization of the ESCRT-I trafficking complex | journal = Cell | volume = 125 | issue = 1 | pages = 113–26 | date = April 2006 | pmid = 16615894 | pmc = 1576341 | doi = 10.1016/j.cell.2006.01.049 | url = }}
4. ^{{cite journal | vauthors = Katzmann DJ, Odorizzi G, Emr SD | title = Receptor downregulation and multivesicular-body sorting | journal = Nat. Rev. Mol. Cell Biol. | volume = 3 | issue = 12 | pages = 893–905 | year = 2002 | pmid = 12461556 | doi = 10.1038/nrm973 }}
5. ^{{cite journal | vauthors = von Schwedler UK, Stuchell M, Müller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Kräusslich HG, Kaplan J, Morham SG, Sundquist WI | title = The protein network of HIV budding | journal = Cell | volume = 114 | issue = 6 | pages = 701–13 | year = 2003 | pmid = 14505570 | doi = 10.1016/S0092-8674(03)00714-1 | url = http://linkinghub.elsevier.com/retrieve/pii/S0092867403007141 }}
6. ^{{cite journal | vauthors = Sun Z, Pan J, Hope WX, Cohen SN, Balk SP | title = Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300 | journal = Cancer | volume = 86 | issue = 4 | pages = 689–96 | date = August 1999 | pmid = 10440698 | doi = 10.1002/(sici)1097-0142(19990815)86:4<689::aid-cncr19>3.0.co;2-p}}
7. ^¹²{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
8. ^{{cite journal | vauthors = Lu Q, Hope LW, Brasch M, Reinhard C, Cohen SN | title = TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 13 | pages = 7626–31 | date = June 2003 | pmid = 12802020 | pmc = 164637 | doi = 10.1073/pnas.0932599100 }}
9. ^{{cite journal | vauthors = Amit I, Yakir L, Katz M, Zwang Y, Marmor MD, Citri A, Shtiegman K, Alroy I, Tuvia S, Reiss Y, Roubini E, Cohen M, Wides R, Bacharach E, Schubert U, Yarden Y | title = Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding | journal = Genes Dev. | volume = 18 | issue = 14 | pages = 1737–52 | date = July 2004 | pmid = 15256501 | pmc = 478194 | doi = 10.1101/gad.294904 }}
10. ^{{cite journal | vauthors = Oh H, Mammucari C, Nenci A, Cabodi S, Cohen SN, Dotto GP | title = Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 8 | pages = 5430–5 | date = April 2002 | pmid = 11943869 | pmc = 122786 | doi = 10.1073/pnas.082123999 }}
11. ^{{cite journal | vauthors = Li L, Liao J, Ruland J, Mak TW, Cohen SN | title = A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 4 | pages = 1619–24 | date = February 2001 | pmid = 11172000 | pmc = 29306 | doi = 10.1073/pnas.98.4.1619 }}
12. ^{{cite journal | vauthors = Stuchell MD, Garrus JE, Müller B, Stray KM, Ghaffarian S, McKinnon R, Kräusslich HG, Morham SG, Sundquist WI | title = The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding | journal = J. Biol. Chem. | volume = 279 | issue = 34 | pages = 36059–71 | date = August 2004 | pmid = 15218037 | doi = 10.1074/jbc.M405226200 }}
13. ^{{cite journal | vauthors = Bishop N, Woodman P | title = TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes | journal = J. Biol. Chem. | volume = 276 | issue = 15 | pages = 11735–42 | date = April 2001 | pmid = 11134028 | doi = 10.1074/jbc.M009863200 }}