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Akt-ing on Regulated Gene Transcription

Science's STKE  18 Oct 2005:
Vol. 2005, Issue 306, pp. tw370
DOI: 10.1126/stke.3062005tw370

Methylation of histone residues in chromatin plays a crucial role in the regulation of gene expression and other chromatin-dependent processes: For example, the methyltransferase enhancer of Zeste homolog 2 (EZH2), a Polycomb group protein, methylates lysine 27 in histone H3 and generally represses transcription. Cell signaling pathways are also critical for many cellular processes: For example, the phosphoinositide 3-kinase Akt (PI3K-Akt) pathway is also implicated in oncogenesis and promotes cell proliferation and represses apoptosis. Cha et al. now link these signaling and gene regulation pathways by showing that the Akt kinase interacts with and down-regulates the H3K27 methyltransferase activity of EZH2. A highly conserved serine residue is phosphorylated, which reduces the affinity of the protein for chromatin and up-regulates the target genes.

T.-L. Cha, B. P. Zhou, W. Xia, Y. Wu, C.-C. Yang, C.-T. Chen, B. Ping, A. P. Otte, M.-C. Hung, Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 310, 306-310 (2005). [Abstract] [Full Text]