title: PARP-1 activation in the ERK signaling pathway.
abstract: PARP-1 is a highly conserved DNA-binding protein, the most abundant member of the polyADP-ribose polymerases (PARP) family, which catalyzes post-translational modification of proteins by polyADP-ribosylation. This modification affects protein-protein and protein-DNA interactions. Binding of PARP-1 to breakages in damaged DNA causes its activation and auto-polyADP-ribosylation in a process that is pivotal for DNA repair. Our recent findings outlined an alternative mechanism of PARP-1 activation via a direct interaction with phosphorylated ERK2 (externally regulated kinase), which is unrelated to DNA damage and does not involve PARP-1 binding to DNA. Furthermore, ERK2-induced PARP-1 activation dramatically amplifies ERK-signals, enhancing ERK-induced phosphorylation of the transcription factor Elk1 and enhancing core histone acetylation and expression of the Elk1 target gene, c-fos. Thus, PARP-1 activation in the ERK signaling pathway mediates epigenetic mechanisms promoting growth, proliferation and differentiation regulated by the Raf-MEK-ERK phosphorylation cascade.
authors.affiliation: Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel. marmon@post.tau.ac.il
authors.forename: Malka
authors.initials: M
authors.lastname: Cohen-Armon
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D008954:Models, Biological; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases