Role of PARP-1 and PARP-2 in the expression of apoptosis-regulating genes in HeLa cells.
Poly (ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding enzyme involved in DNA damage processing, apoptosis, and genetic stability. Many lines of evidence suggest that PARP-1 is implicated in transcriptional regulation of various genes through the modulation of chromatin structure or through direct interaction with transcription factors and/or transcription factor-binding sites. In the present study, we applied TaqMan Low-Density Array analyses to investigate the expression of genes involved in apoptotic cell death induced by an alkylating agent. Using RNA interference, we determined the roles of PARP-1 and PARP-2 in transcriptional regulation during apoptosis in HeLa cells. Of the 93 genes monitored, 33 differentially expressed genes were identified after induction of apoptosis. Whereas the down-regulation of PARP-1 and PARP-2 had no impact on gene expression per se, we observed that Bcl10, c-Rel, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and -2 are differentially expressed after induction of apoptosis in a PARP-1-dependent manner. These findings suggest that PARP-1-but not PARP-2-is required for proper expression of major genes involved in regulation of apoptosis.
Cohausz
Odile
O
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
Althaus
Felix R
FR
D000477:Alkylating Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D000477:Alkylating Agents; D008769:Methylnitronitrosoguanidine; C499320:PARP1 protein, human; C483041:PARP2 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases