Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.
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."
Cheung
Wang L
WL
Department of Microbiology, University of Virginia Health System, Charlottesville 22908, USA.
Ajiro
Kozo
K
Samejima
Kumiko
K
Kloc
Malgorzata
M
Cheung
Peter
P
Mizzen
Craig A
CA
Beeser
Alexander
A
Etkin
Laurence D
LD
Chernoff
Jonathan
J
Earnshaw
William C
WC
Allis
C David
CD
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
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