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

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Myocyte Enhancer Factor 2C (MEF2C) is a transcription factor crucial for skeletal muscle differentiation.
• The regulation of MEF2C during cell division is not well understood.

Purpose of the Study:

• To investigate the role of MEF2C degradation during mitosis.
• To identify the mechanisms regulating MEF2C during the cell cycle.
• To explore the function of MEF2C beyond muscle differentiation.

Main Methods:

• Mitotic degradation assays
• Identification of D-box and phospho-motifs on MEF2C
• Analysis of MEF2C interaction with APC/C and CDC20
• Myoblast culture and gene expression analysis
• Cell proliferation assays in colon cancer cells

Main Results:

• MEF2C is degraded by the APC/C in proliferating cells during mitosis.
• Degradation requires a D-box and two phospho-motifs (pSer98, pSer110) on MEF2C.
• These motifs mediate interaction with CDC20, an APC/C co-activator.
• MEF2C regulates G2/M checkpoint genes and Cyclin B1 localization in myoblasts.
• Modulating MEF2C affects colon cancer cell proliferation.

Conclusions:

• MEF2C degradation by APC/C is a novel mechanism regulating cell cycle progression.
• MEF2C acts as a cell cycle regulator in addition to its role in muscle differentiation.
• MEF2C levels are critical for controlling cell proliferation rates.