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J. Biol. Chem., Vol. 278, Issue 12, 10588-10593, March 21, 2003
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From the Hormel Institute, University of Minnesota,
Austin, Minnesota 55912
Arsenite is known to be an environmental human
carcinogen. However, the mechanism of action of this compound in skin
carcinogenesis is not completely clear. Here, we provide evidence that
arsenite can induce phosphorylation of histone H3 at serine 10 in a
time- and dose-dependent manner in JB6 Cl 41 cells.
Arsenite induces phosphorylation of Akt1 at serine 473 and increases
Akt1 activity. A dominant-negative mutant of Akt1 inhibits the
arsenite-induced phosphorylation of histone H3 at serine 10. Additionally, active Akt1 kinase strongly phosphorylates histone H3 at
serine 10 in vitro. The arsenite-induced phosphorylation of
histone H3 at serine 10 was almost completely blocked by a
dominant-negative mutant of extracellular signal-regulated
kinase 2 and the mitogen-activated protein kinase/extracellular
signal-regulated kinase inhibitor PD98059. N- or C-terminal mutant
mitogen- and stress-activated protein kinase 1 or its inhibitor H89 had
no effect on arsenite-induced phosphorylation of histone H3 at serine
10 in JB6 Cl 41 cells. However, cells deficient in p90 ribosomal S6
kinase 2 (Rsk2
Arsenite-induced Phosphorylation of Histone H3 at
Serine 10 Is Mediated by Akt1, Extracellular Signal-regulated Kinase 2, and p90 Ribosomal S6 Kinase 2 but Not Mitogen- and Stress-activated
Protein Kinase 1*
/) totally block this
phosphorylation in a dose- and time-dependent manner. Taken
together, these results suggested that arsenite-induced phosphorylation
of histone H3 at serine 10 is mediated by Akt1, extracellular
signal-regulated kinase 2 and p90 ribosomal S6 kinase 2 but not
mitogen- and stress-activated protein kinase 1.
*
This work was supported in part by The Hormel Foundation and
by National Institutes of Health Grants CA81064, CA77646, and CA88961.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: 801 16th Ave. NE,
Austin, MN 55912. Tel.: 507-437-9600; Fax: 507-437-9606; E-mail: zgdong@hi.umn.edu.
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