Characterization and function of PARP10 in the control of cell physiology

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The transfer of ADP-ribose from NAD+ to substrate proteins is a highly conserved posttranslational mechanism, implicated in a broad range of biological processes, including bacterial pathogenesis, intracellular signaling, cell division, gene transcription, DNA repair, and apoptosis. Mono-ADP-ribosyltransferases (mARTs) and poly-ADP-ribose polymerases (PARPs) depend on a highly conserved glutamate residue in the active center for catalysis. The PARP family with 17 members is the major class of intracellular ADP-ribosylating enzymes. Unexpectedly, we found that PARP10 (contrary to its name) has mART activity and lacks the catalytic glutamate. Our evidence suggests that PARP10, and presumably other PARPs, ADP-ribosylate acidic residues using substrate-assisted catalysis, explaining why PARP10 cannot generate polymers. In addition we have identified PARP10 foci that might share components with P bodies and stress granules. To understand the function of PARP10 we intend to validate and characterize recently identified potential substrates. Furthermore we plan to investigate the substrate specificity of PARP10 and to generate modification-specific antibodies. We expect that the detailed analysis of PARP10 will have model character for the analysis of intracellular mARTs and help to illuminate the different biological functions of mono- versus poly-ADP-ribosylation.