PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells.
PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells.
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DOI：
10.1038/onc.2011.339
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发表时间：
2012-03-22
期刊：
影响因子：
8
通讯作者：
Nikiforov, M. A.
中科院分区：
文献类型：
--
作者：
Mannava, S.;Omilian, A. R.;Wawrzyniak, J. A.;Fink, E. E.;Zhuang, D.;Miecznikowski, J. C.;Marshall, J. R.;Soengas, M. S.;Sears, R. C.;Morrison, C. D.;Nikiforov, M. A.
Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for 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 up-regulated at the protein level, and largely due to 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 to normal melanocytes. Accordingly, immuno-histochemical 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 up-regulated C-MYC protein levels and suppressed BRAFV600E- and, less efficiently, NRASQ61R-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.
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影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
DOI：
10.1073/pnas.0900121106
发表时间：
2010-01-05
影响因子：
11.1
作者：
Hydbring, Per;Bahram, Fuad;Larsson, Lars-Gunnar
通讯作者：
Larsson, Lars-Gunnar
影响因子：
10.5
作者：
Grandori, C;Wu, KJ;Mormat, RJ
通讯作者：
Mormat, RJ
影响因子：
10.3
作者：
Khanna, Anchit;Bockelman, Camilla;Ristimaki, Ari
通讯作者：
Ristimaki, Ari