TSG101

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Tumor susceptibility 101
Protein TSG101 PDB 1kpp.png
PDB rendering based on 1kpp.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TSG101 ; TSG10; VPS23
External IDs OMIM601387 MGI106581 HomoloGene4584 ChEMBL: 6157 GeneCards: TSG101 Gene
RNA expression pattern
PBB GE TSG101 201758 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7251 22088
Ensembl ENSG00000074319 ENSMUSG00000014402
UniProt Q99816 Q61187
RefSeq (mRNA) NM_006292 NM_021884
RefSeq (protein) NP_006283 NP_068684
Location (UCSC) Chr 11:
18.49 – 18.55 Mb
Chr 7:
46.89 – 46.92 Mb
PubMed search [1] [2]

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

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]

HIV[edit]

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),[2] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.[3]

Interactions[edit]

TSG101 has been shown to interact with HGS,[4][5] P53,[6] EP300,[7] VPS28,[4][8][9] LRSAM1[4][10] and P21.[11]

Orthologue, Vps23[edit]

Vps23_core
PDB 2caz EBI.jpg
escrt-i core
Identifiers
Symbol Vps23_core
Pfam PF09454
InterPro IPR017916

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[edit]

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.

Function[edit]

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.[12][13]

See also[edit]

References[edit]

  1. ^ "Entrez Gene: TSG101 tumor susceptibility gene 101". 
  2. ^ Katzmann DJ, Odorizzi G, Emr SD (2002). "Receptor downregulation and multivesicular-body sorting". Nat. Rev. Mol. Cell Biol. 3 (12): 893–905. doi:10.1038/nrm973. PMID 12461556. 
  3. ^ 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 (2003). "The protein network of HIV budding". Cell 114 (6): 701–13. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570. 
  4. ^ a b c Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  5. ^ Lu, Quan; Hope Lila Weiqiao; Brasch Michael; Reinhard Christoph; Cohen Stanley N (June 2003). "TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (13): 7626–31. doi:10.1073/pnas.0932599100. ISSN 0027-8424. PMC 164637. PMID 12802020. 
  6. ^ Li, L; Liao J; Ruland J; Mak T W; Cohen S N (February 2001). "A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (4): 1619–24. doi:10.1073/pnas.98.4.1619. ISSN 0027-8424. PMC 29306. PMID 11172000. 
  7. ^ Sun, Z; Pan J; Hope W X; Cohen S N; Balk S P (August 1999). "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer (UNITED STATES) 86 (4): 689–96. doi:10.1002/(SICI)1097-0142(19990815)86:4<689::AID-CNCR19>3.0.CO;2-P. ISSN 0008-543X. PMID 10440698. 
  8. ^ Stuchell, Melissa D; Garrus Jennifer E; Müller Barbara; Stray Kirsten M; Ghaffarian Sanaz; McKinnon Rena; Kräusslich Hans-Georg; Morham Scott G; Sundquist Wesley I (August 2004). "The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding". J. Biol. Chem. (United States) 279 (34): 36059–71. doi:10.1074/jbc.M405226200. ISSN 0021-9258. PMID 15218037. 
  9. ^ Bishop, N; Woodman P (April 2001). "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. (United States) 276 (15): 11735–42. doi:10.1074/jbc.M009863200. ISSN 0021-9258. PMID 11134028. 
  10. ^ Amit, Ido; Yakir Liat, Katz Menachem, Zwang Yaara, Marmor Mina D, Citri Ami, Shtiegman Keren, Alroy Iris, Tuvia Shmuel, Reiss Yuval, Roubini Eli, Cohen Maya, Wides Ron, Bacharach Eran, Schubert Ullrich, Yarden Yosef (July 2004). "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding". Genes Dev. (United States) 18 (14): 1737–52. doi:10.1101/gad.294904. ISSN 0890-9369. PMC 478194. PMID 15256501. 
  11. ^ Oh, Hyesun; Mammucari Cristina; Nenci Arianna; Cabodi Sara; Cohen Stanley N; Dotto G Paolo (April 2002). "Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1)". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (8): 5430–5. doi:10.1073/pnas.082123999. ISSN 0027-8424. PMC 122786. PMID 11943869. 
  12. ^ Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB, Vallis Y, Emr SD, Williams RL (April 2006). "ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes". Cell 125 (1): 99–111. doi:10.1016/j.cell.2006.01.047. PMID 16615893. 
  13. ^ Kostelansky MS, Sun J, Lee S, Kim J, Ghirlando R, Hierro A, Emr SD, Hurley JH (April 2006). "Structural and functional organization of the ESCRT-I trafficking complex". Cell 125 (1): 113–26. doi:10.1016/j.cell.2006.01.049. PMC 1576341. PMID 16615894. 

Further reading[edit]