Glycogen Synthase Kinase (GSK) 3β Phosphorylates and Protects Nuclear Myosin 1c from Proteasome-Mediated Degradation to Activate rDNA Transcription in Early G1 Cells

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Nuclear actin and myosin are essential regulators of gene expression. At the exit of mitosis, nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by modulating assembly of the chromatin remodeling complex WICH with the subunits WSTF and SNF2h and, crucially, facilitating H3K9 acetylation by the histone acetyl transferase PCAF. The molecular mechanism by which NM1 is regulated remains however unknown. Here, we conducted a genome-wide screen and demonstrate that GSK3β is selectively coupled to the rDNA transcription unit. In embryonic fibroblasts lacking GSK3β there is a significant drop in rRNA synthesis levels and the rDNA is devoid of actin, NM1 and SNF2h. Concomitantly with a transcriptional block we reveal decreased levels of histone H3 acetylation by the histone acetyl transferase PCAF. At G1, transcriptional repression in the GSK3β knockout mouse embryonic fibroblasts, leads to NM1 ubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β suppresses NM1 degradation through the ubiquitin-proteasome system, facilitates NM1 association with the rDNA chromatin and transcription activation at G1. We therefore propose a novel and fundamental role for GSK3β as essential regulator of rRNA synthesis and cell cycle progression.

Vyšlo v časopise: Glycogen Synthase Kinase (GSK) 3β Phosphorylates and Protects Nuclear Myosin 1c from Proteasome-Mediated Degradation to Activate rDNA Transcription in Early G1 Cells. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004390
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004390

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