title: WEE1 tyrosine kinase, a novel epigenetic modifier.
abstract: The cell cycle requires cells to duplicate their chromatin, DNA, and histones, while retaining a subset of epigenetic marks, in a highly coordinated manner. The WEE1 kinase was identified as an important regulator during S phase, preventing entry into mitosis until DNA replication has been completed. Interestingly, WEE1 has also emerged as a key player in regulating histone synthesis. It phosphorylates histone H2B at tyrosine 37 in the nucleosomes found upstream of the histone gene cluster, and this suppresses histone transcription in late S phase. These observations highlight a dual role for WEE1 as both a mitotic gatekeeper and a surveyor of chromatin synthesis, providing a direct link between epigenetics and cell-cycle progression. Importantly, this link has implications for the design of novel epigenetic inhibitors targeting cancers that display elevated expression of this kinase.
authors.affiliation: Drug Discovery Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. kiran.mahajan@moffitt.org
authors.forename: Kiran
authors.initials: K
authors.lastname: Mahajan
authors.forename: Nupam P
authors.initials: NP
authors.lastname: Mahajan
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004261:DNA Replication; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D005819:Genetic Markers; D006657:Histones; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human
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