TY - JOUR
T1 - PKC zeta controls DNA topoisomerase-dependent human caspase-2 pre-mRNA splicing
AU - Solier, Stéphanie
AU - De Cian, Marie Cécile
AU - Bettaieb, Ali
AU - Desoche, Lydie
AU - Solary, Eric
AU - Corcos, Laurent
N1 - Funding Information:
The authors wish to thank Drs. J. Moscat and M.T. Diaz-Meco (Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma, Cantoblanco, Madrid, Spain) for providing mutated PKC zeta-containing plasmids, Dr. G. Baier (Institute for Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, Austria) for providing mutated PKC alpha-containing plasmids, M. Cortier for her help with cells and Drs. C. Le Jossic-Corcos and Y. Pommier for critical reading of the manuscript. This work was supported by the INSERM, the French Ministry of Research and Education, the Medical Faculties of Dijon and Brest, the Universities of Dijon and Brest, the Ecole Pratique des Hautes Etudes and the Ligue Contre le Cancer. Stéphanie Solier was appointed by the University Hospital of Dijon. Marie-Cécile de Cian was recipient of a post-doctoral fellowship from the General Council of the Brittany region.
PY - 2008/1/23
Y1 - 2008/1/23
N2 - Caspase-2 exists as two main isoforms: the caspase-2L long isoform, which is pro-apoptotic, and the caspase-2S short isoform, which may be anti-apoptotic. Topoisomerase inhibitors drive inclusion of exon 9, specific for Casp-2S mRNA, and lower Casp-2S mRNA and protein. With cell lines engineered to express various PKC isoforms, we demonstrate that PKC zeta, but not PKCalpha, positively regulates Casp-2S mRNA assembly triggered by topoisomerase inhibitors. In addition, exon 9 inclusion is lowered in mitosis but increased in the G1/S phase. Hence, the control of caspase-2 exon 9 inclusion by topoisomerase inhibitors depends on phosphorylation and/or dephosphorylation events, and on the cell cycle phase.
AB - Caspase-2 exists as two main isoforms: the caspase-2L long isoform, which is pro-apoptotic, and the caspase-2S short isoform, which may be anti-apoptotic. Topoisomerase inhibitors drive inclusion of exon 9, specific for Casp-2S mRNA, and lower Casp-2S mRNA and protein. With cell lines engineered to express various PKC isoforms, we demonstrate that PKC zeta, but not PKCalpha, positively regulates Casp-2S mRNA assembly triggered by topoisomerase inhibitors. In addition, exon 9 inclusion is lowered in mitosis but increased in the G1/S phase. Hence, the control of caspase-2 exon 9 inclusion by topoisomerase inhibitors depends on phosphorylation and/or dephosphorylation events, and on the cell cycle phase.
KW - Caspase-2
KW - Cell cycle
KW - PKC zeta
KW - Topoisomerase
KW - mRNA splicing
UR - http://www.scopus.com/inward/record.url?scp=38049086171&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2007.12.032
DO - 10.1016/j.febslet.2007.12.032
M3 - Article
C2 - 18166155
AN - SCOPUS:38049086171
SN - 0014-5793
VL - 582
SP - 372
EP - 378
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -