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

A Tinel, MJ Eckert, E Logette, Saskia Lippens UGent, Sophie Janssens UGent, B Jaccard, M Quadroni and J Tschopp (2011) CELL DEATH AND DIFFERENTIATION. 18(3). p.506-515
abstract
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-kappa B activation. PIDDosome activation is dependent on auto-processing 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-kappa B 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
NF-kappa B, PIDD, Hsp90, Caspase-2, KAPPA-B ACTIVATION, DOMAIN-CONTAINING PROTEIN, CASPASE-2 ACTIVATION, PROTEASOMAL DEGRADATION, P53-INDUCED PROTEIN, GENOTOXIC STRESS, COMPLEX, APOPTOSIS, RECEPTOR, PIDDOSOME
journal title
CELL DEATH AND DIFFERENTIATION
Cell Death Differ.
volume
18
issue
3
pages
506 - 515
Web of Science type
Article
Web of Science id
000287311100012
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
8.849 (2011)
JCR rank
23/286 (2011)
JCR quartile
1 (2011)
ISSN
1350-9047
DOI
10.1038/cdd.2010.124
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1202569
handle
http://hdl.handle.net/1854/LU-1202569
date created
2011-04-05 13:16:31
date last changed
2016-12-19 15:38:07
@article{1202569,
  abstract     = {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-kappa B activation. PIDDosome activation is dependent on auto-processing 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-kappa B 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.},
  author       = {Tinel, A and Eckert, MJ and Logette, E and Lippens, Saskia and Janssens, Sophie and Jaccard, B and Quadroni, M and Tschopp, J},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keyword      = {NF-kappa B,PIDD,Hsp90,Caspase-2,KAPPA-B ACTIVATION,DOMAIN-CONTAINING PROTEIN,CASPASE-2 ACTIVATION,PROTEASOMAL DEGRADATION,P53-INDUCED PROTEIN,GENOTOXIC STRESS,COMPLEX,APOPTOSIS,RECEPTOR,PIDDOSOME},
  language     = {eng},
  number       = {3},
  pages        = {506--515},
  title        = {Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90},
  url          = {http://dx.doi.org/10.1038/cdd.2010.124},
  volume       = {18},
  year         = {2011},
}

Chicago
Tinel, A, MJ Eckert, E Logette, Saskia Lippens, Sophie Janssens, B Jaccard, M Quadroni, and J Tschopp. 2011. “Regulation of PIDD Auto-proteolysis and Activity by the Molecular Chaperone Hsp90.” Cell Death and Differentiation 18 (3): 506–515.
APA
Tinel, A, Eckert, M., Logette, E., Lippens, S., Janssens, S., Jaccard, B., Quadroni, M., et al. (2011). Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90. CELL DEATH AND DIFFERENTIATION, 18(3), 506–515.
Vancouver
1.
Tinel A, Eckert M, Logette E, Lippens S, Janssens S, Jaccard B, et al. Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90. CELL DEATH AND DIFFERENTIATION. 2011;18(3):506–15.
MLA
Tinel, A, MJ Eckert, E Logette, et al. “Regulation of PIDD Auto-proteolysis and Activity by the Molecular Chaperone Hsp90.” CELL DEATH AND DIFFERENTIATION 18.3 (2011): 506–515. Print.