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oai:repisalud.isciii.es:20.500.12105/254502025-12-18T12:55:56Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Mannava, S author Omilian, A R author Wawrzyniak, J A author Fink, E E author Zhuang, D author Miecznikowski, J C author Marshall, J R author Soengas, MS author Sears, R C author Morrison, C D author Nikiforov, M A author 2012-03-22 Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for the suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here we report that C-MYC in cells from several randomly chosen melanoma lines was upregulated at the protein level, and largely because of the increased protein stability. Of all known regulators of C-MYC stability, levels of B56α subunit of the PP2A tumor suppressor complex were substantially suppressed in all human melanoma cells compared with normal melanocytes. Accordingly, immunohistochemical analysis revealed that the lowest and the highest amounts of PP2A-B56α were predominantly detected in metastatic melanoma tissues and in primary melanomas from patients with good clinical outcome, respectively. Importantly, PP2A-B56α overexpression suppressed C-MYC in melanoma cells and induced OIS, whereas depletion of PP2A-B56α in normal human melanocytes upregulated C-MYC protein levels and suppressed BRAF(V600E)- and, less efficiently, NRAS(Q61R)-induced senescence. Our data reveal a mechanism of C-MYC overexpression in melanoma cells and identify a functional role for PP2A-B56α in OIS of melanocytic cells. Oncogene . 2012 Mar 22;31(12):1484-92. Oncogene https://pmc.ncbi.nlm.nih.gov/articles/PMC3213274/pdf/nihms309532.pdf 21822300 https://hdl.handle.net/20.500.12105/25450 senescence PP2A melanoma C-MYC PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells.