Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Aishe A. Sarshad, Martin Corcoran, Bader Al-Muzzaini, Laura Borgonovo-Brandter, Anne Von Euler, Douglas Lamont, Neus Visa, Piergiorgio Percipalle (Lead / Corresponding author)

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    Abstract

    Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3ß phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3ß selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3ß-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3ß directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3ß-mediated phosphorylation of NM1 is required for pol I transcription activation.
    Original languageEnglish
    Article numbere1004390
    Number of pages17
    JournalPLoS Genetics
    Volume10
    Issue number6
    DOIs
    Publication statusPublished - 5 Jun 2014

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    Sarshad, A. A., Corcoran, M., Al-Muzzaini, B., Borgonovo-Brandter, L., Von Euler, A., Lamont, D., Visa, N., & Percipalle, P. (2014). Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells. PLoS Genetics, 10(6), [e1004390]. https://doi.org/10.1371/journal.pgen.1004390