Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition

Cell Cycle
Sara BadodiSusanna Molinari

Abstract

The Myocyte Enhancer Factor 2C (MEF2C) transcription factor plays a critical role in skeletal muscle differentiation, promoting muscle-specific gene transcription. Here we report that in proliferating cells MEF2C is degraded in mitosis by the Anaphase Promoting Complex/Cyclosome (APC/C) and that this downregulation is necessary for an efficient progression of the cell cycle. We show that this mechanism of degradation requires the presence on MEF2C of a D-box (R-X-X-L) and 2 phospho-motifs, pSer98 and pSer110. Both the D-box and pSer110 motifs are encoded by the ubiquitous alternate α1 exon. These two domains mediate the interaction between MEF2C and CDC20, a co-activator of APC/C. We further report that in myoblasts, MEF2C regulates the expression of G2/M checkpoint genes (14-3-3γ, Gadd45b and p21) and the sub-cellular localization of CYCLIN B1. The importance of controlling MEF2C levels during the cell cycle is reinforced by the observation that modulation of its expression affects the proliferation rate of colon cancer cells. Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation.

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Citations

Dec 10, 2015·Cellular and Molecular Life Sciences : CMLS·H Rudolf de BoerMarcel A T M van Vugt
Jun 3, 2016·Cellular and Molecular Life Sciences : CMLS·H Rudolf de BoerMarcel A T M van Vugt
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May 9, 2018·Journal of Cellular Biochemistry·Chundi GaoChanggang Sun
Mar 15, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Robert J ShuteDustin R Slivka
Jan 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Srinadh ChopparaManas Kumar Santra
May 21, 2019·Oncotarget·Kiran MadugulaPooja Jain
Jul 16, 2020·International Journal of Molecular Sciences·Estephania Zluhan-MartínezAdriana Garay-Arroyo
Oct 4, 2017·Endocrinology·Teruyo Nakatani, Nicola C Partridge
Jan 28, 2021·Nucleic Acids Research·Matthew K TannerCharles A Thornton
Apr 27, 2021·Physiological Genomics·Jinchao LiSonia S Kupfer

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Methods Mentioned

BETA
flow cytometry
PCR
transfection
immunoprecipitation
reverse transcription PCR
nuclear translocation
transfections
electrophoresis
co-immunoprecipitation
Assay

Software Mentioned

Image J
ClustalW

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