title: Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.
abstract: DNA in eukaryotic cells is associated with histone proteins; hence, hallmark properties of apoptosis, such as chromatin condensation, may be regulated by posttranslational histone modifications. Here we report that phosphorylation of histone H2B at serine 14 (S14) correlates with cells undergoing programmed cell death in vertebrates. We identify a 34 kDa apoptosis-induced H2B kinase as caspase-cleaved Mst1 (mammalian sterile twenty) kinase. Mst1 can phosphorylate H2B at S14 in vitro and in vivo, and the onset of H2B S14 phosphorylation is dependent upon cleavage of Mst1 by caspase-3. These data reveal a histone modification that is uniquely associated with apoptotic chromatin in species ranging from frogs to humans and provide insights into a previously unrecognized physiological substrate for Mst1 kinase. Our data provide evidence for a potential apoptotic "histone code."
authors.affiliation: Department of Microbiology, University of Virginia Health System, Charlottesville 22908, USA.
authors.forename: Wang L
authors.initials: WL
authors.lastname: Cheung
authors.forename: Kozo
authors.initials: K
authors.lastname: Ajiro
authors.forename: Kumiko
authors.initials: K
authors.lastname: Samejima
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
authors.forename: Peter
authors.initials: P
authors.lastname: Cheung
authors.forename: Craig A
authors.initials: CA
authors.lastname: Mizzen
authors.forename: Alexander
authors.initials: A
authors.lastname: Beeser
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Etkin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation / Q000235:genetics; D005057:Eukaryotic Cells / Q000201:enzymology*; D018922:HL-60 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D053148:Caspase 3; D020169:Caspases; D002843:Chromatin; D004247:DNA; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012694:Serine; C095566:STK4 protein, human; D000099317:Hippo Kinases; C505407:CASP3 protein, human