What deubiquitinating enzymes, oncogenes, and tumor suppressors actually do: Are current assumptions supported by patient outcomes?. (7th January 2021)

• Record Type: Journal Article
• Authors: Gregoire‐Mitha, Sophie; Gray, Douglas A.
• Is Part Of: BioEssays. Volume 43:Number 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-01-07
• Subjects: deubiquitinating enzyme -- oncogene -- survival curve -- TGF‐β paradox -- tumor suppressor -- UCHL1 -- USP4; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000269
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Context can determine whether a given gene acts as an oncogene or a tumor suppressor. Deubiquitinating enzymes (DUBs) regulate the stability of many components of the pathways dictating cell fate so it would be expected that alterations in the levels or activity of these enzymes may have oncogenic or tumor suppressive consequences. In the current review we survey publications reporting that genes encoding DUBs are oncogenes or tumor suppressors. For many DUBs both claims have been made. For such "double agents, " the effects of gain or loss of function will depend on the overall status of a complex of molecular signaling networks subject to extensive crosstalk. As the TGF‐β paradox makes clear context is critical in cell fate decisions, and the disconnect between experimental findings and patient survival outcomes can in part be attributed to disparities between culture conditions and the microenvironment in vivo. Convincing claims for oncogene or tumor suppressor roles require the documentation of gene alterations in patient samples; survival curves are alone inadequate. Abstract : A deubiquitinating enzyme (DUB) can exert oncogenic or antioncogenic activity based on input received from molecular networks. Such networks integrate multiple inputs dictated by the cell microenvironment. A DUB gene can therefore be described as a "double agent" with properties of an oncogene or tumor suppressor depending on context.