PKC zeta controls DNA topoisomerase-dependent human caspase-2 pre-mRNA splicing.
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-2L [corrected] 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.
Solier
Stéphanie
S
INSERM U517, Faculty of Medicine, Dijon, France.
De Cian
Marie-Cécile
MC
Bettaieb
Ali
A
Desoche
Lydie
L
Solary
Eric
E
Corcos
Laurent
L
D017398:Alternative Splicing; D053143:Caspase 2 / Q000378:metabolism*; D026942:DNA Topoisomerases / Q000378:metabolism*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells; D000099221:Protein Kinase C zeta
D053143:Caspase 2; D026942:DNA Topoisomerases; D011493:Protein Kinase C; D012322:RNA Precursors; D012333:RNA, Messenger; D000099221:Protein Kinase C zeta