Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade.

TitlePositioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade.
Publication TypeJournal Article
Year of Publication1997
AuthorsBerra E, Municio MM, Sanz L, Frutos S, Diaz-Meco MT, Moscat J
JournalMol Cell Biol
Date Published1997 Aug
Keywords3T3 Cells, Animals, Apoptosis, Apoptosis Regulatory Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Caspase 1, COS Cells, Cysteine Endopeptidases, Humans, Intracellular Signaling Peptides and Proteins, Mice, Protein Kinase C, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Protein p53, Ultraviolet Rays

Recent studies have documented the involvement of the atypical protein kinase C (aPKC) isoforms in important cellular functions such as cell proliferation and survival. Exposure of cells to a genotoxic stimulus that induces apoptosis, such as UV irradiation, leads to a profound inhibition of the atypical PKC activity in vivo. In this study, we addressed the relationship between this phenomenon and different proteins involved in the apoptotic response. We show that (i) the inhibition of the aPKC activity precedes UV-induced apoptosis; (ii) UV-induced aPKC inhibition and apoptosis are independent of p53; (iii) Bcl-2 proteins are potent modulators of aPKC activity; and (iv) the aPKCs are located upstream of the interleukin-converting enzyme-like protease system, which is required for the induction of apoptosis by both Par-4 (a selective aPKC inhibitor) and UV irradiation. We also demonstrate here that inhibition of aPKC activity leads to a decrease in mitogen-activated protein (MAP) kinase activity and simultaneously an increase in p38 activity. Both effects are critical for the induction of apoptosis in response to Par-4 expression and UV irradiation. Collectively, these results clarify the position of the aPKCs in the UV-induced apoptotic pathway and strongly suggest that MAP kinases play a role in this signaling cascade.

Alternate JournalMol Cell Biol
PubMed ID9234692
PubMed Central IDPMC232288
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700