Are PARPs promiscuous?

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Post-translational modifications regulate cellular functions, with ADP-ribosylation by poly(ADP-ribose) polymerases (PARPs) being crucial for cell health.
• PARPs can transfer single ADP-ribose (MARylation) or poly(ADP-ribose) (PAR) chains to various amino acid residues, expanding beyond traditional targets like arginine and glutamate.
• While PARP1's function is well-studied, the roles and specific targets of other PARPs, such as PARP7 and PARP10, are less understood.

Purpose of the Study:

• To review the current understanding of PARP enzyme specificity in vitro and in cellular contexts.
• To highlight the expanding repertoire of amino acid residues modified by ADP-ribosylation.
• To identify knowledge gaps and propose future research directions for elucidating PARP functions.

Main Methods:

• Literature review of existing studies on PARP enzymatic activity and substrate specificity.
• Analysis of recent findings on novel ADP-ribose acceptor amino acids.
• Discussion of known and unknown hydrolases involved in reversing ADP-ribosylation.

Main Results:

• ADP-ribosylation occurs on a wider range of amino acids than previously thought, including serine, tyrosine, and histidine.
• Specific hydrolases like ARH1, ARH3, MACROD1, MACROD2, and TARG1 reverse ADP-ribosylation on certain residues, but not all.
• The endogenous targets and precise biological functions of many PARP family members remain to be identified.

Conclusions:

• Further research is needed to identify the endogenous targets of various PARPs.
• Understanding the biochemical reactions and specificities of PARPs is essential for deciphering their roles in cellular processes.
• Elucidating PARP functions will advance our knowledge of cell health maintenance and disease mechanisms.