PARP12 functions under stess conditions

PARP12 is a protein belonging to a family of enzymes known as poly(ADPribosyl)polymerases (PARPs), that are able to transfer ADP-ribose units from NAD+ molecules onto protein targets post-translationally. Some of these enzymes catalyze poly-ADP-ribose (PAR) chain formation on specific substrates while others can only transfer a single unit of ADP-ribose. Only recently, the functions of these mono-ADP-ribosyl tranferases (mARTs) are starting to emerge. With the aim to study PARP functions, we analysed the enzymatic activities of these enzymes and found that, among the others, PARP12 showed a robust catalytic activity. Therefore we focused on PARP12. The knowledge on PARP12 refers to its role in protection from viral infection and inhibition of protein translation during stress responses. It has been demonstrated that the over-expression of PARP12 causes the formation of the stress granules, cytoplasmic structures involved in the decision of a cell to enter or not apoptosis. In our laboratory we have shown that under oxidative stress endogenous PARP12 moves from the Golgi complex to the stress granules (SGs). Based on this evidence, we investigated the molecular mechanism underlying this process and the role of the protein at SGs. In details, we have elucidated the molecular determinants of this translocation by a structural-functional analysis and identified the domains required for this translocation. In addition, our data clarified the role of the enzyme at the SGs, where its catalytic activity is required for the regulation of apoptosis.