The PIDDosome, DNA-damage-induced apoptosis and beyond

Abstract

P53-induced protein with a death domain (PIDD) was cloned as a death domain (DD)-containing protein whose expression is induced by p53. It was later described as the core of a molecular platform-activating caspase-2, named the PIDDosome. These first results pointed towards a role for PIDD in apoptosis, in response to DNA damage. Identification of new PIDDosome complexes involved in DNA repair and nuclear factor-jB signaling challenged this early concept. PIDD functions are growing as new complexes and new interaction partners are being discovered, and as additional functions are being revealed. A fascinating feature of PIDD lies within its complex and tight regulation mechanisms, which allow the molecule to fine-tune its different functions: from transcriptional regulation to the expression of different isoforms, and from the interaction with regulatory proteins to an ingenious post-translational cleavage mechanism generating various active fragments with specific functions. Further studies still need to be carried out to provide answers to many unresolved issues and to reconcile conflicting results. This review aims at providing an overview of the current PIDD knowledge status.

Apoptosis induced by lipid-associated membrane proteins from Mycoplasma hyopneumoniae in a porcine lung epithelial cell line with the involvement of caspase 3 and the MAPK pathway

“…At the beginning of apoptosis, the 116-kDa PARP protein is inactivated by cleavage into 24-and 89-kDa fragments by caspase 3, leaving it unable to effect the repair of damaged DNA. The activity of Ca 2+ /Mg 2+ -dependent endonuclease DNAS1L3 increases, and it is regulated by PARP; this causes increased cleavage of chromosomal DNA leading to apoptosis (Janssens and Tinel, 2012). Caspase 8 also plays an important role in apoptosis.…”

Cell Death and Cancer, Novel Therapeutic Strategies

“…PIDD associates with RAIDD, forming a signalling platform known as the PIDDosome [53]. The PIDDosome can activate caspase-2 and the transcription factor NFkB in response to DNA damage [54]. Caspase-2 acts upstream of the mitochondria by inducing Bid cleavage, Bax translocation and cytochrome c release.…”

IAPs, TNF, inflammation and Jürg TSCHOPP; a personal perspective

“…21 I was also given unlimited access to the phenomenal collection of reagents that Pascal Schneider had assembled. Along with other helpful lab mates like Margot Thome, Etienne Meylan, Antoine Tinel and Sophie Janssens who have contributed a review on the Piddosome to this edition, 22 it was obvious that another of Jü rg's talents was to assemble great scientists around him. I was surprised to find that Jü rg regularly wandered into the lab, not to check whether people were still at work, but to explore some 'crazy' idea he'd just had.…”