| RRC ID |
42340
|
| 著者 |
Moro T, Ogasawara T, Chikuda H, Ikeda T, Ogata N, Maruyama Z, Komori T, Hoshi K, Chung UI, Nakamura K, Okayama H, Kawaguchi H.
|
| タイトル |
Inhibition of Cdk6 expression through p38 MAP kinase is involved in differentiation of mouse prechondrocyte ATDC5.
|
| ジャーナル |
J Cell Physiol
|
| Abstract |
Because a temporal arrest in the G1-phase of the cell cycle is a prerequisite for cell differentiation, this study investigated the involvement of cell cycle factors in the differentiation of cultured mouse prechondrocyte cell line ATDC5. Among the G1 cell cycle factors examined, both protein and mRNA levels of cyclin-dependent kinase (Cdk6) were downregulated during the culture in a differentiation medium. The protein degradation of Cdk6 was not involved in this downregulation because proteasome inhibitors did not reverse the protein level. When inhibitors of p38 MAPK, ERK-1/2, and PI3K/Akt were added to the culture, only a p38 MAPK inhibitor SB203580 blocked the decrease in the Cdk6 protein level by the differentiation medium, indicating that the Cdk6 inhibition was mediated by p38 MAPK pathway. In fact, p38 MAPK was confirmed to be phosphorylated during differentiation of ATDC5 cells. Enforced expression of Cdk6 in ATDC5 cells blocked the chondrocyte differentiation and inhibited Sox5 and Sox6 expressions. However, the Cdk6 overexpression did not affect the proliferation or the cell cycle progression, suggesting that the inhibitory effect of Cdk6 on the differentiation was exerted by a mechanism largely independent of its cell cycle regulation. These results indicate that Cdk6 may be a regulator of chondrocyte differentiation and that its p38-mediated downregulation is involved in the efficient differentiation.
|
| 巻・号 |
204(3)
|
| ページ |
927-33
|
| 公開日 |
2005-9-1
|
| DOI |
10.1002/jcp.20350
|
| PMID |
15795936
|
| MeSH |
Animals
Cell Cycle
Cell Differentiation*
Cell Line, Tumor
Chondrocytes / cytology*
Chondrocytes / enzymology*
Chondrocytes / metabolism
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinases / genetics
Cyclin-Dependent Kinases / metabolism*
Down-Regulation*
Gene Expression
Mice
Signal Transduction
p38 Mitogen-Activated Protein Kinases / metabolism*
|
| IF |
5.546
|
| 引用数 |
16
|
|
WOS 分野
|
PHYSIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
