TSG101
Description
The TSG101 (tumor susceptibility 101) is a protein-coding gene located on chromosome 11.
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. 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. 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.
TSG101, a component of the ESCRT-I complex, plays a crucial role in regulating vesicular trafficking. It binds to ubiquitinated cargo proteins, facilitating the sorting of endocytosed ubiquitinated cargos into multivesicular bodies (MVBs). TSG101 mediates the association between the ESCRT-0 and ESCRT-I complexes and is essential for the completion of cytokinesis, a process that requires its interaction with CEP55. TSG101 may also influence cell growth and differentiation, acting as a negative growth regulator. Furthermore, TSG101 participates in the budding of various viruses by interacting with viral proteins containing a late-budding motif P-[ST]-A-P. This interaction is critical for the budding of numerous retroviruses. TSG101 is required for the exosomal release of SDCBP, CD63, and syndecan, and may contribute to the release of microvesicles distinct from exosomes.
TSG101 is also known as TSG10, VPS23.
