TSG101

TSG101

TSG101 (Tumor Susceptibility Gene 101) is a protein encoded by the TSG101 gene in humans. It is a component of the endosomal sorting complex required for transport (ESCRT) machinery, which is involved in the sorting of ubiquitinated proteins into multivesicular bodies (MVBs) and in the budding of certain enveloped viruses. TSG101 plays a crucial role in cellular processes such as cell cycle regulation, signal transduction, and the maintenance of genomic stability.

Structure

The TSG101 protein contains several functional domains that are essential for its role in the ESCRT-I complex. These include the ubiquitin E2 variant (UEV) domain, which is involved in binding ubiquitin, and the proline-rich region, which facilitates interactions with other proteins. The structure of TSG101 allows it to interact with various partners, including ubiquitin and other components of the ESCRT machinery.

Function

TSG101 is a key player in the ESCRT-I complex, which is responsible for the sorting of ubiquitinated membrane proteins into the intraluminal vesicles of MVBs. This process is critical for the degradation of membrane proteins in the lysosome. TSG101 also participates in the budding of certain viruses, such as HIV, from the host cell membrane, making it a target for antiviral therapies.

In addition to its role in protein sorting, TSG101 is involved in regulating the cell cycle and maintaining genomic stability. It has been implicated in the control of cytokinesis, the final step of cell division, and in the response to DNA damage.

Clinical Significance

Mutations or dysregulation of TSG101 have been associated with various cancers, as it is involved in pathways that control cell proliferation and survival. The loss of TSG101 function can lead to genomic instability, a hallmark of cancer. Research is ongoing to understand the potential of TSG101 as a therapeutic target in cancer treatment.

Research and Applications

TSG101 is a subject of intense research due to its involvement in critical cellular processes and its potential as a target for therapeutic intervention. Studies are exploring its role in viral budding, cancer progression, and its interactions with other proteins in the ESCRT pathway.

Also see

• ESCRT machinery
• Ubiquitin
• Multivesicular body
• HIV
• Cell cycle

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