PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response.

Poly(ADP-ribose) polymerases also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs  , , ). regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that Pduanyu37s also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by As is the case for other Pduanyu37s that function during stress, the enzymatic activity of Pduanyu3716 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by Pduanyu3716 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by Pduanyu3716 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of Pduanyu3716 is required for Pduanyu3716 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic catalytic domain.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}