TSG101

From Wikipedia, the free encyclopedia

Tumor susceptibility gene 101

PDB rendering based on 1kpp.

Available structures: 1kpp, 1kpq, 1m4p, 1m4q, 1s1q, 2f0r

Identifiers

Symbol(s)

TSG101; TSG10; VPS23

External IDs

OMIM: 601387 MGI: 106581 HomoloGene: 4584

Gene ontology
Molecular Function:	• DNA binding • transcription corepressor activity • ubiquitin-protein ligase activity • protein binding
Cellular Component:	• membrane
Biological Process:	• regulation of cell growth • ubiquitin cycle • cell cycle arrest • negative regulation of cell proliferation • protein transport • keratinocyte differentiation • negative regulation of transcription, DNA-dependent

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_006292 (mRNA)
NP_006283 (protein)

NM_021884 (mRNA)
NP_068684 (protein)

Location

Chr 11: 18.46 - 18.51 Mb

Chr 7: 46.76 - 46.79 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]

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

[edit] References

^ Entrez Gene: TSG101 tumor susceptibility gene 101.
^ 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.
^ 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. PMID 14505570.

[edit] Further reading

Mazzé FM, Degrève L (2006). "The role of viral and cellular proteins in the budding of human immunodeficiency virus.". Acta Virol. 50 (2): 75–85. PMID 16808324.
Freed EO, Mouland AJ (2006). "The cell biology of HIV-1 and other retroviruses.". Retrovirology 3: 77. doi:10.1186/1742-4690-3-77. PMID 17083721.
Li L, Li X, Francke U, Cohen SN (1997). "The TSG101 tumor susceptibility gene is located in chromosome 11 band p15 and is mutated in human breast cancer.". Cell 88 (1): 143–54. PMID 9019400.
Koonin EV, Abagyan RA (1997). "TSG101 may be the prototype of a class of dominant negative ubiquitin regulators.". Nat. Genet. 16 (4): 330–1. doi:10.1038/ng0897-330. PMID 9241264.
Steiner P, Barnes DM, Harris WH, Weinberg RA (1997). "Absence of rearrangements in the tumour susceptibility gene TSG101 in human breast cancer.". Nat. Genet. 16 (4): 332–3. doi:10.1038/ng0897-332. PMID 9241265.
Lee MP, Feinberg AP (1997). "Aberrant splicing but not mutations of TSG101 in human breast cancer.". Cancer Res. 57 (15): 3131–4. PMID 9242438.
Gayther SA, Barski P, Batley SJ, et al. (1997). "Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours.". Oncogene 15 (17): 2119–26. doi:10.1038/sj.onc.1201591. PMID 9366528.
Xie W, Li L, Cohen SN (1998). "Cell cycle-dependent subcellular localization of the TSG101 protein and mitotic and nuclear abnormalities associated with TSG101 deficiency.". Proc. Natl. Acad. Sci. U.S.A. 95 (4): 1595–600. PMID 9465061.
Wagner KU, Dierisseau P, Rucker EB, et al. (1998). "Genomic architecture and transcriptional activation of the mouse and human tumor susceptibility gene TSG101: common types of shorter transcripts are true alternative splice variants.". Oncogene 17 (21): 2761–70. doi:10.1038/sj.onc.1202529. PMID 9840940.
Sun Z, Pan J, Hope WX, et al. (1999). "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300.". Cancer 86 (4): 689–96. PMID 10440698.
Hittelman AB, Burakov D, Iñiguez-Lluhí JA, et al. (1999). "Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins.". EMBO J. 18 (19): 5380–8. doi:10.1093/emboj/18.19.5380. PMID 10508170.
Rountree MR, Bachman KE, Baylin SB (2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.". Nat. Genet. 25 (3): 269–77. doi:10.1038/77023. PMID 10888872.
Bishop N, Woodman P (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.
Li L, Liao J, Ruland J, et al. (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. doi:10.1073/pnas.98.4.1619. PMID 11172000.
VerPlank L, Bouamr F, LaGrassa TJ, et al. (2001). "Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag).". Proc. Natl. Acad. Sci. U.S.A. 98 (14): 7724–9. doi:10.1073/pnas.131059198. PMID 11427703.
Garrus JE, von Schwedler UK, Pornillos OW, et al. (2001). "Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.". Cell 107 (1): 55–65. PMID 11595185.
Martin-Serrano J, Zang T, Bieniasz PD (2002). "HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress.". Nat. Med. 7 (12): 1313–9. doi:10.1038/nm1201-1313. PMID 11726971.
Demirov DG, Ono A, Orenstein JM, Freed EO (2002). "Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function.". Proc. Natl. Acad. Sci. U.S.A. 99 (2): 955–60. doi:10.1073/pnas.032511899. PMID 11805336.
Bennett NA, Pattillo RA, Lin RS, et al. (2002). "TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.". Cell. Mol. Biol. (Noisy-le-grand) 47 (7): 1187–93. PMID 11838966.
Bishop N, Horman A, Woodman P (2002). "Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates.". J. Cell Biol. 157 (1): 91–101. doi:10.1083/jcb.200112080. PMID 11916981.