Histone H1(S)-3 phosphorylation in Ha-ras oncogene-transformed mouse fibroblasts.
Oncogene
; 21(55): 8397-403, 2002 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-12466960
ABSTRACT
Phosphorylation of linker histone H1(S)-3 (previously named H1b) and core histone H3 is elevated in mouse fibroblasts transformed with oncogenes or constitutively active mitogen-activated protein kinase (MAPK) kinase (MEK). H1(S)-3 phosphorylation is the only histone modification known to be dependent upon transcription and replication. Our results show that the increased amounts of phosphorylated H1(S)-3 in the oncogene Ha-ras-transformed mouse fibroblasts was a consequence of an elevated Cdk2 activity rather than the reduced activity of a H1 phosphatase, which our studies suggest is PP1. Induction of oncogenic ras expression results in an increase in H1(S)-3 and H3 phosphorylation. However, in contrast to the phosphorylation of H3, which occurred immediately following the onset of Ras expression, there was a lag of several hours before H1(S)-3 phosphorylation levels increased. We found that there was a transient increase in the levels of p21(cip1), which inhibited the H1 kinase activity of Cdk2. Cdk2 activity and H1(S)-3 phosphorylated levels increased after p21(cip1) levels declined. Our studies suggest that persistent activation of the Ras-MAPK signal transduction pathway in oncogene-transformed cells results in deregulated activity of kinases phosphorylating H3 and H1(S)-3 associated with transcribed genes. The chromatin remodelling actions of these modified histones may result in aberrant gene expression.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linhagem Celular Transformada
/
Histonas
/
Genes ras
/
Quinases relacionadas a CDC2 e CDC28
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article