Document Detail


Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation.
MedLine Citation:
PMID:  15994958     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
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.    
Journal Detail:
Title:  Cancer research     Volume:  65     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-04     Completed Date:  2005-09-07     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5818-27     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
CA77646/CA/NCI NIH HHS; CA81064/CA/NCI NIH HHS; R01 CA077646/CA/NCI NIH HHS; R01 CA081064/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Histones; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Transcription Factor AP-1; 452VLY9402/Serine; 62229-50-9/Epidermal Growth Factor
Comments/Corrections

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