
-   Tsg101 interacts with Tsg101-associated ligase (Tal), a RING E3 ubiquitin ligase. Tal induces mono-ubiquitination of Tsg101's C-terminal, toggling it between an active membrane-bound form and an inactive soluble form. Further investigations reveal Tal's role in Tsg101 level regulation by targeting excessive Tsg101 for proteasomal degradation. This is achieved through polyubiquitination of lysines in the C-terminal region, overlapping with Tsg101's stability-determining region. However, Tsg101's polyubiquitination is inhibited when it binds to other ESCRT-I subunits, possibly due to the concealment of target lysines or physical interference with the Tal/Tsg101/ubiquitin complex formation [PMID: 18077552].
-   In murine NIH3T3 fibroblasts, antisense inactivation of tsg101 gene, encoding TSG101 protein, leads to neoplastic transformation, which is reversed by restoring TSG101 activity. Overproduction of TSG101 from chromosomally inserted constructs causes compensatory down-regulation of endogenous TSG101 mRNA, with the adventitious TSG101 replacing the native protein. This regulation of TSG101 protein levels involves a conserved sequence near its COOH-terminal, termed the "steadiness box," suggesting a self-regulated proteolysis or a proteolytic feedback-control mechanism [PMID: 10749147].
-   TSG101 mRNA is strongly upregulated in conditionally immortalized mouse podocytes by cyclic mechanical stress. In DOCA/salt treated rats, a model of glomerular hypertension, glomerular TSG101 mRNA levels are elevated in podocytes [PMID: 30782301].
