PIDD1

PIDD1 contains a leucine-rich repeat and a death domain. This protein has been shown to interact with other death domain proteins, such as Fas (TNFRSF6)-associated via death domain (FADD) and MAP-kinase activating death domain-containing protein (MADD), and thus may function as an adaptor protein in cell death-related signaling processes. The expression of the mouse counterpart of this gene has been found to be positively regulated by the tumor suppressor p53 and to induce cell apoptosis in response to DNA damage, which suggests a role for this gene as an effector of p53-dependent apoptosis.

Full Name

P53-Induced Death Domain Protein 1

Function

Component of the DNA damage/stress response pathway that functions downstream of p53/TP53 and can either promote cell survival or apoptosis (PubMed:10973264, PubMed:15073321, PubMed:16360037, PubMed:17159900).
Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis (PubMed:15073321, PubMed:17159900).
Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B (PubMed:16360037, PubMed:17159900).

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestManual Assertion Based On ExperimentIMP:UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptorsIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentTAS:UniProtKB
Protein autoprocessingManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Cytoplasm
Nucleus
Enriched in the nucleus upon DNA damage.

PTM

Undergoes autoproteolytic processing whose extent either directs cells towards survival or apoptotic pathways (PubMed:17159900).
Autoproteolytically cleaved into two main fragments PIDD-N and PIDD-C (PubMed:17159900).
PIDD-C can be further processed into PIDD-CC, a processing which is enhanced by DNA damage (PubMed:17159900).
The cleavage producing PIDD-C is required for translocation of PIDD1 to the nucleus upon DNA damage and activation of NF-kappa-B (PubMed:17159900).
PIDD-CC mediates the interaction with CRADD and the cleavage producing PIDD-CC is required for the activation of CASP2 (PubMed:17159900).
PIDD-N remains associated with PIDD-C and PIDD-CC after cleavage (PubMed:17159900).