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

Abstract

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, wild-type 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 Ser10 is an essential regulatory mechanism for EGF-induced neoplastic cell transformation.

• Authors: Hong Seok Choi, Bu Young Choi, Yong-Yeon Cho, Hideya Mizuno, Bong Seok Kang, Ann M Bode, Zigang Dong
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 13 Pg. 5818-27 (Jul 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15994958 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histones
• Proto-Oncogene Proteins c-fos
• Proto-Oncogene Proteins c-jun
• RNA, Messenger
• RNA, Small Interfering
• Transcription Factor AP-1
• Serine
• Epidermal Growth Factor

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Cell Transformation, Neoplastic (drug effects, genetics, metabolism)
• Epidermal Growth Factor (pharmacology)
• Epithelial Cells (metabolism, physiology)
• Gene Expression Regulation
• Genes, fos (genetics)
• Genes, jun (genetics)
• Histones (antagonists & inhibitors, genetics, metabolism)
• Mice
• Molecular Sequence Data
• Phosphorylation
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-fos (antagonists & inhibitors, biosynthesis, genetics, physiology)
• Proto-Oncogene Proteins c-jun (antagonists & inhibitors, biosynthesis, genetics, physiology)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Serine (metabolism)
• Transcription Factor AP-1 (metabolism)