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

Zhiwei He, Wei Ya Ma, Guangming Liu, Yiguo Zhang, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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 Aktl at serine 473 and increases Akt1 activity. A dominant-negative mutant of Aktl inhibits the arsenite-induced phosphorylation of histone H3 at serine 10. Additionally, active Aktl 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-/-) 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 Aktl, extracellular signal-regulated kinase 2 and p90 ribosomal S6 kinase 2 but not mitogen- and stress-activated protein kinase 1.

Original languageEnglish (US)
Pages (from-to)10588-10593
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number12
DOIs
StatePublished - Mar 21 2003

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