Identification and analysis of dominant negative mutants of RAIDD and PIDD

Tae Ho Jang, Ju Young Bae, Ok Kyoung Park, Ji Hoe Kim, Kyung Hyun Cho, Ju-Hong Jeon, Hyun Ho Park

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Caspases are cysteine proteases that are essential during the initiation and execution of apoptosis and inflammation. The formation of large oligomeric protein complexes is critical to the activation of caspases in apoptotic and inflammatory signaling pathways. These oligomeric protein complexes function as a platform to recruit caspases, which leads to caspase activation via a proximity-induced mechanism. One well-known oligomeric caspase-activating complex is the PIDDosome for caspase-2 activation, which is composed of 3 protein components, PIDD, RAIDD and Caspase-2. Despite the significant role that caspase-2 activated by PIDDosome plays during genotoxic stress-induced apoptosis, the oligomerization mechanism and the method by which the caspase-activating process is mediated by the formation of PIDDosome is currently not well understood. Here, we show that the assembly mechanism of the core of PIDDosome is time-dependent and salt concentration-dependent. In addition, we demonstrate that point mutations on RAIDD (R147E) and on PIDD (Y814A) exert a dominant negative effect on the formation of the PIDDosome, and that this effect cannot be applied after the PIDDosome has been formed. Crown

Original languageEnglish
Pages (from-to)1557-1563
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1804
Issue number7
DOIs
StatePublished - 1 Jul 2010

Fingerprint

Caspases
Caspase 2
Chemical activation
Apoptosis
Oligomerization
Proteins
Cysteine Proteases
Crowns
Point Mutation
DNA Damage
Salts
Inflammation

Keywords

  • Apoptosis
  • Apoptosome
  • Caspase-2
  • DISC
  • Dominant negative mutant
  • Inflammation
  • PIDD PIDDosome
  • RAIDD

Cite this

Jang, Tae Ho ; Bae, Ju Young ; Park, Ok Kyoung ; Kim, Ji Hoe ; Cho, Kyung Hyun ; Jeon, Ju-Hong ; Park, Hyun Ho. / Identification and analysis of dominant negative mutants of RAIDD and PIDD. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2010 ; Vol. 1804, No. 7. pp. 1557-1563.
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Identification and analysis of dominant negative mutants of RAIDD and PIDD. / Jang, Tae Ho; Bae, Ju Young; Park, Ok Kyoung; Kim, Ji Hoe; Cho, Kyung Hyun; Jeon, Ju-Hong; Park, Hyun Ho.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1804, No. 7, 01.07.2010, p. 1557-1563.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification and analysis of dominant negative mutants of RAIDD and PIDD

AU - Jang, Tae Ho

AU - Bae, Ju Young

AU - Park, Ok Kyoung

AU - Kim, Ji Hoe

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AU - Jeon, Ju-Hong

AU - Park, Hyun Ho

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