Pidd1
Domain
The Death domain mediates the interaction with CRADD and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn recruit 7 CASP2 to form the PIDDosome.
The LRR repeat-containing domain has a regulatory activity, being autoinhibitory for the activation of NF-kappa-B.
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). Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis. Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B (By similarity).
Post-translational modifications
Undergoes autoproteolytic processing whose extent either directs cells towards survival or apoptotic pathways. Autoproteolytically cleaved into two main fragments PIDD-N and PIDD-C. PIDD-C can be further processed into PIDD-CC, a processing which is enhanced by DNA damage. The cleavage producing PIDD-C is required for translocation of PIDD1 to the nucleus upon DNA damage and activation of NF-kappa-B. PIDD-CC mediates the interaction with CRADD and the cleavage producing PIDD-CC is required for the activation of CASP2. PIDD-N remains associated with PIDD-C and PIDD-CC after cleavage.
Tissue Specificity
Ubiquitous.
Cellular localization
- Cytoplasm
- Nucleus
- Enriched in the nucleus upon DNA damage.
Alternative names
Lrdd, Pidd, Pidd1, p53-induced death domain-containing protein 1, Leucine-rich repeat and death domain-containing protein