Biochemical characterization of MSK1 as a transcriptional coactivator of p53 in the p21 gene regulation

Abstract

Gene transcription is regulated by transcription factors and coactivators. Mitogen and stress activated protein kinase (MSK1) is phosphorylated by upstream signal stimulation, which makes intramolecular phosphorylation to have an active form. Active MSK1 stimulates transcription by phosphorylation of histone serine residues. The tumor suppressor gene, p53, is a transcription factor of several target genes, and there are reports that it is involved in transcriptional regulation by interacting with several kinase proteins, but the specific mechanism is not known. This study revealed that MSK1 and p53 directly binds in vitro and in cells, and found that the coactivator MSK1 was recruited to the promoter region of the p53 target gene p21 to increase its transcription. In addition, we made 35 phosphomimic mutants of MSK1, revealing that hydrophobic motifs in the linker region are important for MSK activity. This study shows that p53 and MSK1 act cooperatively in the transcriptional regulation of p21, and that intracellular phosphorylation of MSK1 plays an important role in its activation.