p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress

Cuenin, Solange; Tinel, Antoine; Janssens, Sophie; Tschopp, Jürg

doi:10.1038/sj.onc.1210635

Cited by 53 publications

(59 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These isoforms have been described to exhibit different functions, for example, isoform-2 is thought to counteract isoform-1-driven proapoptotic effects. 39 Further studies are underway to investigate whether the differential interactions of Hsp90 and Hsp70 with the isoforms have functional consequences.…”

Section: Discussionmentioning

confidence: 99%

Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90

et al. 2010

Self Cite

View full text Add to dashboard Cite

In response to DNA damage, p53-induced protein with a death domain (PIDD) forms a complex called the PIDDosome, which either consists of PIDD, RIP-associated protein with a death domain and caspase-2, forming a platform for the activation of caspase-2, or contains PIDD, RIP1 and NEMO, important for NF-jB activation. PIDDosome activation is dependent on autoprocessing of PIDD at two different sites, generating the fragments PIDD-C and PIDD-CC. Despite constitutive cleavage, endogenous PIDD remains inactive. In this study, we screened for novel PIDD regulators and identified heat shock protein 90 (Hsp90) as a major effector in both PIDD protein maturation and activation. Hsp90, together with p23, binds PIDD and inhibition of Hsp90 activity with geldanamycin efficiently disrupts this association and impairs PIDD auto-processing. Consequently, both PIDD-mediated NF-jB and caspase-2 activation are abrogated. Interestingly, PIDDosome formation itself is associated with Hsp90 release. Characterisation of cytoplasmic and nuclear pools of PIDD showed that active PIDD accumulates in the nucleus and that only cytoplasmic PIDD is bound to Hsp90. Finally, heat shock induces Hsp90 release from PIDD and PIDD nuclear translocation. Thus, Hsp90 has a major role in controlling PIDD functional activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Three isoforms of PIDD differentially activate NF-kB and caspase-2 in response to genotoxic stress (Cuenin et al, 2008). Thus, PIDD may act as a molecule switch controlling the balance between cell survival and cell death in response to DNA damage.…”

Section: Piddosome and Caspase-2 Activationmentioning

confidence: 99%

Caspases in apoptosis and beyond

2008

View full text Add to dashboard Cite

“…123 So far, three isoforms of PIDD have been described, of which all are capable of activating NF-kB upon DNA damage, but only isoform 1 interacts with RAIDD/ CRADD and activate caspase-2. 124 RAIDD/CRADD cell death-unrelated functions are still poorly characterized, but may include the regulation of (at least some) differentiation programs. 125 Notably, raidd À/À mice are not viable, yet this presumably depends on RAIDD/CRADD involvement in apoptosis-mediated embryo remodeling rather than in other processes (as assessed by its expression pattern during organogenesis, which correlates with profound morphological changes occurring in the developing embryo).…”

Section: Vital Functions Of Cell Death-related Adaptor Moleculesmentioning

confidence: 99%

No death without life: vital functions of apoptotic effectors

et al. 2008

View full text Add to dashboard Cite

As a result of the genetic experiments performed in Caenorhabditis elegans, it has been tacitly assumed that the core proteins of the 'apoptotic machinery' (CED-3, -4, -9 and EGL-1) would be solely involved in cell death regulation/execution and would not exert any functions outside of the cell death realm. However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. Similarly, loss-of-function mutations of ced-4 compromise the mitotic arrest of DNA-damaged germline cells from adult nematodes, even in a context in which the apoptotic machinery is inoperative (for instance due to mutations of egl-1 or ced-3). Moreover, EGL-1 is required for the activation of autophagy in starved nematodes. Finally, the depletion of caspaseindependent death effectors, such as apoptosis-inducing factor (AIF) and endonuclease G, provokes cell death-independent consequences, both in mammals and in yeast (Saccharomyces cerevisiae). These results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosisunrelated function, most likely as part of an adaptive response to cellular stress.

show abstract

p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress

Cited by 53 publications

References 21 publications

Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90

Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90

Caspases in apoptosis and beyond

No death without life: vital functions of apoptotic effectors

Contact Info

Product

Resources

About