Mutant p53 induces SIRT3/MnSOD axis to moderate ROS production in melanoma cells

Show simple item record Torrens-Mas, M. Cordani, M. Mullappilly, N. Pacchiana, R. Riganti, C. Palmieri, M. Pons, D.G. Roca, P. Oliver, J. Donadelli, M. 2024-02-07T07:18:12Z 2024-02-07T07:18:12Z
dc.description.abstract The TP53 tumor suppressor gene is the most frequently altered gene in tumors and mutant p53 isoforms can acquire oncogenic properties referred to as gain-of-function (GOF). In this study, we used wild-type (A375) and mutant p53 (MeWo) melanoma cell lines to assess the regulation of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD) by mutant p53. The effects of mutant p53 were evaluated by qPCR, immunoblotting, enzyme activity assay, cell proliferation assay, reactive oxygen species (ROS) assay after cellular transfection. We demonstrate that mutant p53 induces MnSOD expression, which is recovered by the ROS scavenger N-acetyl-l-cysteine. This suggests MnSOD induction as a defense mechanism of melanoma cells to counterbalance the pro-oxidant conditions induced by mutant p53. We also demonstrate that mutant p53 induces the expression of Sirtuin3 (SIRT3), a major mitochondrial NAD+-dependent deacetylase, stimulating MnSOD deacetylation and enzymatic activity. Indeed, the restoration of SIRT3 reverses MnSOD activity decrease by mutant p53 knock-down. Finally, MnSOD knock-down further enhances mutant p53-mediated ROS increase, counteracting mutp53-dependent cell hyperproliferation. This indicates that SIRT3 and MnSOD act to maintain ROS levels controlled to promote cell proliferation and survival, providing new therapeutic opportunities to be further considered for clinical studies in cancer patients bearing mutant TP53 gene.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Archives of Biochemistry and Biophysics, 2020, vol. 679, p. 108219
dc.subject.classification 57 - Biologia
dc.subject.classification Ciències de la salut
dc.subject.other 57 - Biological sciences in general
dc.subject.other Medical sciences
dc.title Mutant p53 induces SIRT3/MnSOD axis to moderate ROS production in melanoma cells
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2024-02-07T07:18:13Z
dc.subject.keywords ROS
dc.subject.keywords Mutant p53
dc.subject.keywords Cancer
dc.subject.keywords SIRT3
dc.subject.keywords MnSOD
dc.rights.accessRights info:eu-repo/semantics/openAccess

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