Abstract
The multidomain protein encoded by the Tumor Susceptibility Gene 101 (TSG101) is ubiquitously expressed and is suggested to function in diverse intracellular processes. In this review, we provide a succinct overview of the main structural features of the protein and their suggested roles in molecular and cellular functions. We then summarize, in more detail, key findings from studies using genetically engineered animal models that demonstrate essential functions of TSG101 in cell proliferation and survival, normal tissue homeostasis, and tumorigenesis. Despite studies on cell lines that provide insight into the molecular underpinnings by which TSG101 might function as a negative growth regulator, a biologically significant role of TSG101 as a tumor suppressor has yet to be confirmed using genuine in vivo cancer models. More recent observations from several cancer research teams suggest that TSG101 might function as an oncoprotein. A potential role of post-translational mechanisms that control the expression of the TSG101 protein in cancer is being discussed. In the final section of the review, we summarize critical issues that need to be addressed to gain a better understanding of biologically significant roles of TSG101 in cancer.
Highlights
Is ubiquitously expressed and is suggested to function in diverse intracellular processes
As controls to the genomic knockout, we examined the level of Tumor Susceptibility Gene 101 (TSG101) in the ‘TSG101-deficient’ SL6 cell line described earlier and were surprised that these cells exhibited only a marginal reduction in the TSG101 protein compared to their parental NIH3T3 cells
TSG101 is suggested to function in a variety of cellular processes, the vast majority of published reports over the past 20 years have highlighted specific molecular mechanisms by which TSG101 may control the intracellular trafficking of cargo proteins such as receptor tyrosine kinases (RTKs) and viral particles
Summary
The coding sequences of the mouse and human TSG101 mRNAs are 86% identical on the nucleotide level [2]. Sanger sequencing data generated by our team revealed that the genomic organization of the Tsg101 locus is highly conserved between mouse and human [8], and the mRNA transcripts span across 10 exons and not six as previously reported. TATA and CAAT boxes, and the highly GC-rich sequence contains several consensus sites for Sp1, AP2, and GAPBF2 [8] In support of this notion, TSG101 is expressed in all tissues and cell types [2,8], and the analysis of expressed sequence tags (ESTs) revealed that the Tsg101 mRNA is already present in 1-cell and 2-cell stage mouse embryos. As discussed later in this review, a tight post-translational control of the TSG101 protein level that balances variations in mRNA expression imposes challenges for the generation of genetically engineered models to assess the effects of TSG101 gain- or loss-of-function in normal organogenesis and cancer development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
