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The Multifaceted Roles of the Tumor Susceptibility Gene 101 (TSG101) in Normal Development and Disease

1
Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, 4100 John R, EL01TM, Detroit, MI 48201, USA
2
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 450; https://doi.org/10.3390/cancers12020450
Received: 14 January 2020 / Revised: 7 February 2020 / Accepted: 10 February 2020 / Published: 14 February 2020
(This article belongs to the Special Issue The Study of Cancer Susceptibility Genes)
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. View Full-Text
Keywords: TSG101 protein; cell death; cell survival; gene deletion; knockout; mouse; mutagenesis; oncogenes; transgenes TSG101 protein; cell death; cell survival; gene deletion; knockout; mouse; mutagenesis; oncogenes; transgenes
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Ferraiuolo, R.-M.; Manthey, K.C.; Stanton, M.J.; Triplett, A.A.; Wagner, K.-U. The Multifaceted Roles of the Tumor Susceptibility Gene 101 (TSG101) in Normal Development and Disease. Cancers 2020, 12, 450.

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