Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation

被引：87

作者：

Choi, HS ^{[1
]}

Choi, BY ^{[1
]}

Cho, YY ^{[1
]}

Mizuno, H ^{[1
]}

Kang, BS ^{[1
]}

Bode, AM ^{[1
]}

Dong, ZG ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

来源：

CANCER RESEARCH | 2005年 / 65卷 / 13期

关键词：

D O I：

10.1158/0008-5472.CAN-05-0197

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Very little is known about the role of histone H3 phosphorylation in malignant transformation and cancer development. Here, we examine the function of H3 phosphorylation in cell transformation in vivo. Introduction of small interfering RNA-H3 into JB6 cells resulted in decreased epidermal growth factor (EGF)-induced cell transformation. In contrast, wildtype histone H3 (H3 WT)-overexpressing cells markedly stimulated EGF-induced cell transformation, whereas the H3 mutant S10A cells suppressed transformation. When H3 WT was overexpressed, EGF induction of c-fos and c-jun promoter activity was significantly increased compared with control cells but not in the H3 mutant S10A or S28A cells. In addition, activator protein-1 activity in H3 WT-overexpressing cells was markedly up-regulated by EGF in contrast to the H3 mutant S10A or S28A cells. These results indicate that the phosphorylation of histone H3 at Ser(10) is an essential regulatory mechanism for EGF-induced neoplastic cell transformation.

引用

页码：5818 / 5827

页数：10

共 53 条

[41] Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3 [J].