TSG101

Last updated
TSG101
Protein TSG101 PDB 1kpp.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TSG101 , TSG10, VPS23, tumor susceptibility 101
External IDs OMIM: 601387; MGI: 106581; HomoloGene: 4584; GeneCards: TSG101; OMA:TSG101 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006292

NM_021884
NM_001348088
NM_001348089

RefSeq (protein)

NP_006283

NP_068684
NP_001335017
NP_001335018

Location (UCSC) Chr 11: 18.47 – 18.53 Mb Chr 7: 46.54 – 46.57 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5]

The main role of TSG101 is to participate in the ESCRT (endosomal sorting complexes required for transport) pathway. This pathway facilitates reverse topology budding and formation of multivesicular bodies (MVB) which deliver cargo destined for degradation to the lysosomes. [6] TSG101 recognises a short linear motif, P(T/S)AP, 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. [7] [8]

Viral hijacking

TSG101 plays an important role in the pathogenesis of HIV and other viruses. In uninfected cells, TSG101 functions in the biogenesis of the multivesicular body (MVB), [9] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding. [10]

Interactions

TSG101 has been shown to interact with:

Orthologue, Vps23

Vps23_core
PDB 2caz EBI.jpg
escrt-i core
Identifiers
SymbolVps23_core
Pfam PF09454
InterPro IPR017916
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000074319 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000014402 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: TSG101 tumor susceptibility gene 101".
  6. Henne WM, Buchkovich NJ, Emr SD (July 2011). "The ESCRT pathway". Developmental Cell. 21 (1): 77–91. doi: 10.1016/j.devcel.2011.05.015 . PMID   21763610.
  7. 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. S2CID   14017291.
  8. 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.
  9. 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. S2CID   1344520.
  10. 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. S2CID   16894972.
  11. Sun Z, Pan J, Hope WX, Cohen SN, Balk SP (August 1999). "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer. 86 (4): 689–96. doi: 10.1002/(sici)1097-0142(19990815)86:4<689::aid-cncr19>3.0.co;2-p . PMID   10440698. S2CID   26971556.
  12. 1 2 3 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
  13. Lu Q, Hope LW, Brasch M, Reinhard C, Cohen SN (June 2003). "TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation". Proc. Natl. Acad. Sci. U.S.A. 100 (13): 7626–31. Bibcode:2003PNAS..100.7626L. doi: 10.1073/pnas.0932599100 . PMC   164637 . PMID   12802020.
  14. 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 (July 2004). "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding". Genes Dev. 18 (14): 1737–52. doi:10.1101/gad.294904. PMC   478194 . PMID   15256501.
  15. Oh H, Mammucari C, Nenci A, Cabodi S, Cohen SN, Dotto GP (April 2002). "Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1)". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5430–5. Bibcode:2002PNAS...99.5430O. doi: 10.1073/pnas.082123999 . PMC   122786 . PMID   11943869.
  16. Li L, Liao J, Ruland J, Mak TW, Cohen SN (February 2001). "A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1619–24. Bibcode:2001PNAS...98.1619L. doi: 10.1073/pnas.98.4.1619 . PMC   29306 . PMID   11172000.
  17. Stuchell MD, Garrus JE, Müller B, Stray KM, Ghaffarian S, McKinnon R, Kräusslich HG, Morham SG, Sundquist WI (August 2004). "The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding". J. Biol. Chem. 279 (34): 36059–71. doi: 10.1074/jbc.M405226200 . PMID   15218037.
  18. Bishop N, Woodman P (April 2001). "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. 276 (15): 11735–42. doi: 10.1074/jbc.M009863200 . PMID   11134028.

Further reading