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Tumor Susceptibility Gene 101 (TSG101) was identified in a random mutagenesis screen for potential tumor suppressors in NIH 3T3 cells. Altered transcripts of this gene have been detected in sporadic breast cancers and many other human malignancies. Though the function of TSG101 is not clearly understood, its protein structure includes motifs involved in transcription regulation, and TSG101 has been shown to modulate the activation of steroid hormone receptors. In addition, TSG101 may have a role in regulating ubiquination. The N-terminal region of TSG101 contains a domain that resembles the catalytically active region of ubiquitin conjugases. However, TSG101 lacks an active-site cysteine crucial to the function of these conjugases. Interestingly, TSG101 interferes with MDM2 ubiquination leading to a decrease in MDM2 decay and down-regulation of p53 protein. Thus, TSG101 may function as a dominant-negative inhibitor of ubiquination in pathways where protein expression is tightly regulated.Western Blotting
