Biology:TSG101

From HandWiki
A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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 TSG101 is to participate in ESCRT pathway. This pathway facilitates reverse topology budding and formation of multivesicular bodies (MVB) which delivers cargo destined for degradation to the lysosomes.[2] TSG101 recognises 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.[3][4]

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),[5] which suggests that HIV may bind TSG101 in order to gain access to the downstream machinery that catalyzes MVB vesicle budding.[6]

Interactions

TSG101 has been shown to interact with:

Orthologue, Vps23

Vps23_core
PDB 2caz EBI.jpg
escrt-i core
Identifiers
SymbolVps23_core
PfamPF09454
InterProIPR017916

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

  • FGI-104 - an ESCRT inhibitor being researched as a broad spectrum antiviral

References

  1. ↑ "Entrez Gene: TSG101 tumor susceptibility gene 101". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7251. 
  2. ↑ "The ESCRT pathway". Developmental Cell 21 (1): 77–91. July 2011. doi:10.1016/j.devcel.2011.05.015. PMID 21763610. 
  3. ↑ "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. April 2006. doi:10.1016/j.cell.2006.01.047. PMID 16615893. 
  4. ↑ "Structural and functional organization of the ESCRT-I trafficking complex". Cell 125 (1): 113–26. April 2006. doi:10.1016/j.cell.2006.01.049. PMID 16615894. 
  5. ↑ "Receptor downregulation and multivesicular-body sorting". Nat. Rev. Mol. Cell Biol. 3 (12): 893–905. 2002. doi:10.1038/nrm973. PMID 12461556. 
  6. ↑ "The protein network of HIV budding". Cell 114 (6): 701–13. 2003. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570. 
  7. ↑ "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer 86 (4): 689–96. August 1999. doi:10.1002/(sici)1097-0142(19990815)86:4<689::aid-cncr19>3.0.co;2-p. PMID 10440698. 
  8. ↑ 8.0 8.1 8.2 "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
  9. ↑ "TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation". Proc. Natl. Acad. Sci. U.S.A. 100 (13): 7626–31. June 2003. doi:10.1073/pnas.0932599100. PMID 12802020. Bibcode: 2003PNAS..100.7626L. 
  10. ↑ "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding". Genes Dev. 18 (14): 1737–52. July 2004. doi:10.1101/gad.294904. PMID 15256501. 
  11. ↑ "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. April 2002. doi:10.1073/pnas.082123999. PMID 11943869. Bibcode: 2002PNAS...99.5430O. 
  12. ↑ "A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1619–24. February 2001. doi:10.1073/pnas.98.4.1619. PMID 11172000. Bibcode: 2001PNAS...98.1619L. 
  13. ↑ "The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding". J. Biol. Chem. 279 (34): 36059–71. August 2004. doi:10.1074/jbc.M405226200. PMID 15218037. 
  14. ↑ "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. 276 (15): 11735–42. April 2001. doi:10.1074/jbc.M009863200. PMID 11134028. 

Further reading




Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:TSG101&oldid=3154302"