Targeting Deubiquitinating Enzymes and Autophagy in Cancer.
Maintenance of proper cellular homeostasis requires constant surveillance and precise regulation of intracellular protein content. Protein monitoring and degradation is performed by two distinct pathways in a cell: the autophage-lysosome pathway and the ubiquitin-proteasome pathway. Protein degradation pathways are frequently dysregulated in multiple cancer types and can be both tumor suppressive and tumor promoting. This knowledge has presented the ubiquitin proteasome system (UPS) and autophagy as attractive cancer therapeutic targets. Deubiquitinating enzymes of the UPS have garnered recent attention in the field of cancer therapeutics due to their frequent dysregulation in multiple cancer types. The content of this chapter discusses reasoning behind and advances toward targeting autophagy and the deubiquitinating enzymes of the UPS in cancer therapy, as well as the compelling evidence suggesting that simultaneous targeting of these protein degradation systems may deliver the most effective, synergistic strategy to kill cancer cells.
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA. sexto117@umn.edu.
Ashley
A
Mooneyham
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
Martina
M
Bazzaro
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D000072017:Deubiquitinating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D054852:Small Molecule Libraries; D025801:Ubiquitin; D000072017:Deubiquitinating Enzymes; D046988:Proteasome Endopeptidase Complex
Autophagy; Cancer; Deubiquitinating enzymes; Small molecule inhibitors; Ubiquitin–proteasome system