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- Title
E2F1 stability is regulated by a novel-PKC/p38β MAP kinase signaling pathway during keratinocyte differentiation.
- Authors
Ivanova, I. A.; D'Souza, S. J. A.; Dagnino, L.
- Abstract
E2F transcription factors regulate proliferation, differentiation, DNA repair and apoptosis. Tight E2F regulation is crucial for epidermal formation and regeneration. However, virtually nothing is known about the molecular events modulating E2F during epidermal keratinocyte differentiation. Elucidation of these events is essential to understand epidermal morphogenesis, transformation and repair. Here we show that, in differentiating keratinocytes, Ca2+-induced protein kinase C (PKC) activation downregulates E2F1 protein levels. Further, we have identified PKCδ and η as those isoforms specifically involved in induction of E2F1 proteasomal degradation. We also demonstrate that E2F1 downregulation by novel PKC isozymes requires activation of p38β mitogen-activated protein kinase (MAPK). This is the first example of regulation in the E2F transcription factor family by activation of PKC and MAPK in the context of biologically significant differentiation stimuli in epithelia.Oncogene (2006) 25, 430–437. doi:10.1038/sj.onc.1208999; published online 22 August 2005
- Subjects
KERATINOCYTES; DNA repair; APOPTOSIS; MITOGEN-activated protein kinases; PROTEIN kinases; EPITHELIAL cells
- Publication
Oncogene, 2006, Vol 25, Issue 3, p430
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208999