Format

Send to

Choose Destination
J Cell Biol. 2005 Feb 14;168(4):561-6. Epub 2005 Feb 7.

CDK4 regulation by TNFR1 and JNK is required for NF-kappaB-mediated epidermal growth control.

Author information

1
Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94304, USA.

Abstract

Nuclear factor kappaB (NF-kappaB) mediates homeostatic growth inhibition in the epidermis, and a loss of NF-kappaB function promotes proliferation and oncogenesis. To identify mechanisms responsible for these effects, we impaired NF-kappaB action in the epidermis by three different genetic approaches, including conditional NF-kappaB blockade. In each case, epidermal hyperplasia was accompanied by an increase in both protein levels and tissue distribution of the G1 cell cycle kinase, CDK4. CDK4 up-regulation required intact TNFR1 and c-Jun NH2-terminal kinase (JNK) function. Cdk4 gene deletion concomitant with conditional NF-kappaB blockade demonstrated that CDK4 is required for growth deregulation. Therefore, epidermal homeostasis depends on antagonist regulation of CDK4 expression by NF-kappaB and TNFR1/JNK.

PMID:
15699216
PMCID:
PMC2171750
DOI:
10.1083/jcb.200411060
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center