Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-β in cells lacking the CDK inhibitor p15

Antonio Lavarone and Joan Massagué
Additional contact information
Antonio Lavarone: Memorial Sloan-Kettering Cancer Center
Joan Massagué: Memorial Sloan-Kettering Cancer Center

Nature, 1997, vol. 387, issue 6631, 417-422

Abstract: Abstract The activity of the cyclin-dependent kinases (CDKs) that control cell growth and division can be negatively regulated by tyrosine phosphorylation or by the binding of various CDK inhibitors1. Whereas regulation by tyrosine phosphorylation is well documented in CDKs that function during mitosis, little is known about its role in the regulation of CDKs that act in the G1 phase of the cell cycle2. In contrast, much evidence has accumulated on the regulation of G1 CDKs by CDK inhibitors1. The cytokine TGF-β inhibits growth by causing cell-cycle arrest as a result of increasing the concentration of the Cdk4/6 inhibitor p15INK4B/MTS2 (refs 3, 4). Here we report that TGF-β can also cause the inhibition of Cdk4 and Cdk6 by increasing their level of tyrosine phosphorylation. Tyrosine phosphorylation and inactivation of Cdk4/6 in a human mammary epithelial cell line are shown to result from the ability of TGF-β to repress expression of the CDK tyrosine phosphatase Cdc25A. Repression of Cdc25A and induction of p15 are independent effects mediating the inhibition of Cdk4/6 by TFG-β.

Date: 1997
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/387417a0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:387:y:1997:i:6631:d:10.1038_387417a0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/387417a0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().