PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells

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...

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Main Authors:	Mannava, Sudha, Omilian, Angela R., Wawrzyniak, Joseph A., Fink, Emily E., Zhuang, Dazhong, Miecznikowski, Jeffrey C., Marshall, James R., Soengas, Maria S., Sears, Rosalie C., Morrison, Carl D., Nikiforov, Mikhail A.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213274/

id	pubmed-3213274
recordtype	oai_dc
spelling	pubmed-32132742012-09-22 PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells Mannava, Sudha Omilian, Angela R. Wawrzyniak, Joseph A. Fink, Emily E. Zhuang, Dazhong Miecznikowski, Jeffrey C. Marshall, James R. Soengas, Maria S. Sears, Rosalie C. Morrison, Carl D. Nikiforov, Mikhail A. Article 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. 2011-08-08 2012-03-22 /pmc/articles/PMC3213274/ /pubmed/21822300 http://dx.doi.org/10.1038/onc.2011.339 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mannava, Sudha Omilian, Angela R. Wawrzyniak, Joseph A. Fink, Emily E. Zhuang, Dazhong Miecznikowski, Jeffrey C. Marshall, James R. Soengas, Maria S. Sears, Rosalie C. Morrison, Carl D. Nikiforov, Mikhail A.
spellingShingle	Mannava, Sudha Omilian, Angela R. Wawrzyniak, Joseph A. Fink, Emily E. Zhuang, Dazhong Miecznikowski, Jeffrey C. Marshall, James R. Soengas, Maria S. Sears, Rosalie C. Morrison, Carl D. Nikiforov, Mikhail A. PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
author_facet	Mannava, Sudha Omilian, Angela R. Wawrzyniak, Joseph A. Fink, Emily E. Zhuang, Dazhong Miecznikowski, Jeffrey C. Marshall, James R. Soengas, Maria S. Sears, Rosalie C. Morrison, Carl D. Nikiforov, Mikhail A.
author_sort	Mannava, Sudha
title	PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
title_short	PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
title_full	PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
title_fullStr	PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
title_full_unstemmed	PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells
title_sort	pp2a-b56α controls oncogene-induced senescence in normal and tumor human melanocytic cells
description	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.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213274/
_version_	1611486850759786496

PP2A-B56α Controls Oncogene-Induced Senescence in Normal and Tumor Human Melanocytic Cells

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