title: A degradative detour for mutant TP53.
abstract: Accumulation of mutant TP53 proteins in cancer cells has been recognized as an important factor that promotes cancer progression and metastasis. Thus, strategies that promote the degradation of mutant TP53 might be beneficial for the treatment of cancers. In a recent issue of Genes & Development, we demonstrated that blocking macroautophagy under nutritional stress condition leads to the degradation of mutant TP53 through activating the chaperone-mediated autophagy (CMA) pathway in nonproliferating cancer cells. We propose CMA as a new degradative mechanism for mutant TP53 and the possibility of activating CMA as a new treatment for cancers with mutant TP53.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA USA.
authors.forename: Helin
authors.initials: H
authors.lastname: Vakifahmetoglu-Norberg
authors.forename: Junying
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D001596:Benzylamines / Q000494:pharmacology; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; D018832:Molecular Chaperones; D050505:Mutant Proteins; D011799:Quinazolines; D016159:Tumor Suppressor Protein p53; C000591235:spautin-1; D046988:Proteasome Endopeptidase Complex
keywords: autophagy; cancer; chaperone-mediated autophagy; mutant TP53; spautin-1