@article{7f6f1fd3c5254f35bbd36580f72aafe8,
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{"}.",
author = "Cheung, {Wang L.} and Kozo Ajiro and Kumiko Samejima and Malgorzata Kloc and Peter Cheung and Mizzen, {Craig A.} and Alexander Beeser and Etkin, {Laurence D.} and Jonathan Chernoff and Earnshaw, {William C.} and Allis, {C. David}",
note = "Funding Information: We thank members of the Allis lab for discussions, Upstate Biotechnology Inc. (UBI; Lake Placid, New York) for assistance in the initial development of the H2B (S14) antibody, Rueyling Lin (UT Southwestern, Dallas, Texas) for testing our antibodies in C. elegan s, and Linda Langman for laboratory managerial support. W.L.C. was supported by the NIH Medical Scientist Training Grant. Initial stages of this work were carried out by K.A., who was supported by a Visiting Scientist gift from UBI. Work in the W.C.E. lab is supported by the NIH and The Wellcome Trust, of which W.C.E. is a Principal Research Fellow. L.D.E. is supported by grants from the NIH and the NSF. This work is supported by NIH grants GM54168 to J.C. and GM40922 to C.D.A. ",
year = "2003",
month = may,
day = "16",
doi = "10.1016/S0092-8674(03)00355-6",
language = "English (US)",
volume = "113",
pages = "507--517",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "4",
}