Molecular Toxicology of Chromatin
Abstract
Intracellular phosphorylation of poly (ADP-ribose) polymerase was assayed in streptolysin-0-permeabilized human lymphocytes. Whereas 32P incorporation from (gamma-32P)ATP into immuno-precipitated enzyme protein was undetectable in resting cells, significant phosphorylation of this enzyme was observed in lymphocytes treated with phytohemagglutinin. The phosphorylation of poly (ADP-ribose) polymerase in permeabilized cells was not stimulated by phorbol ester, but phosphorylation of other proteins and of a specific oligopeptide substrate of protein kinase C was increased by phorbol ester. The specific inhibitory pseudosubstrate peptide of protein kinase C blocked the phosphorylation of poly (ADP-ribose) polymerase induced by phytohemagglutinin. A potential role of a member of the protein kinase C family in the intracellular regulation of poly (ADP-ribose) polymerase by phosphorylation appears probable. The structure of poly (ADP-ribose) polymerase has been augmented by the identification of polypeptide sequences which define histone and self association. Both protein binding domains are components of 64-67 kDa basic moiety of poly ADP-ribose polymerase, obtained by degradation by chymotrypsin or plasmin. Two discrete his tone binding domains are interspersed and contiguous with 'selfbinding domains and are located at 186-290 and 446-525 residues. Self binding is confined to the 29 kDa N-terminal moiety of poly ADP-ribose polymerase and to two smaller polypeptide sequences 291-395 and 526-606 residues. Bound zinc is not required for self binding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 08, 1994
- Accession Number
- ADA279430
Entities
People
- Ernest Kun
Organizations
- San Francisco State University