Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae.
Apoptosis is a highly coordinated cell suicide mechanism in vertebrates. Phosphorylation of serine 14 of histone H2B, catalyzed by Mst1 kinase, has been linked to chromatin compaction during apoptosis. We extend these results to unicellular eukaryotes by demonstrating that H2B is specifically phosphorylated at serine 10 (S10) in a hydrogen peroxide-induced cell death pathway in S. cerevisiae. H2B S10A mutants are resistant to cell death elicited by H(2)O(2) while H2B S10E phospho-site mimics promote cell death and induce the "constitutive" formation of condensed chromatin. Ste20 kinase, a yeast homolog of mammalian Mst1 kinase, translocates into the nucleus in a caspase-independent fashion and directly phosphorylates H2B at S10. Conservation of targeted H2B phosphorylation and the enzyme system responsible for the process point to an ancient mechanism of chromatin remodeling that likely plays an important role in governing cellular homeostasis in a wide range of organisms.
Ahn
Sung-Hee
SH
Laboratory of Chromatin Biology, The Rockefeller University, Box 78, New York, NY 10021, USA.
Cheung
Wang L
WL
Hsu
Jer-Yuan
JY
Diaz
Robert L
RL
Smith
M Mitchell
MM
Allis
C David
CD
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae