Two distinct signalling cascades target the NF-κB regulatory factor c-IAP1 for degradation

Rebecca A. Csomos, Casey Wright, Stefanie Galbán, Karolyn A. Oetjen, Colin S. Duckett

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

c-IAP1 (cellular inhibitor of apoptosis 1) has recently emerged as a negative regulator of the non-canonical NF-κB (nuclear factor κB) signalling cascade. Whereas synthetic IAP inhibitors have been shown to trigger the autoubiquitination and degradation of c-IAP1, less is known about the physiological mechanisms by which c-IAP1 stability is regulated. In the present paper, we describe two distinct cellular processes that lead to the targeted loss of c-IAP1. Recruitment of a TRAF2 (tumour necrosis factor receptor-associated factor 2)-c-IAP1 complex to the cytoplasmic domain of the Hodgkin's/anaplastic large-cell lymphoma-associated receptor, CD30, leads to the targeting and degradation of the TRAF2-c-IAP1 heterodimer through a mechanism requiring the RING (really interesting new gene) domain of TRAF2, but not c-IAP1. In contrast, the induced autoubiquitination of c-IAP1 by IAP antagonists causes the selective loss of c-IAP1, but not TRAF2, thereby releasing TRAF2. Thus c-IAP1 can be targeted for degradation by two distinct processes, revealing the critical importance of this molecule as a regulator of numerous intracellular signalling cascades.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalBiochemical Journal
Volume420
Issue number1
DOIs
StatePublished - May 15 2009
Externally publishedYes

Fingerprint

Corrosion inhibitors
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Apoptosis
Degradation
3'-(1-butylphosphoryl)adenosine
Anaplastic Large-Cell Lymphoma
Hodgkin Disease
Genes
Molecules

Keywords

  • CD30
  • Inhibitor of apoptosis (IAP)
  • Lymphoma
  • Nuclear factor κB (NF-κB)
  • Second mitochondrial-derived activator of caspase (Smac)/ direct inhibitor of apoptosis-binding protein with low pI (DIABLO)
  • Tumour necrosis factor receptor-associated factor (TRAF)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Two distinct signalling cascades target the NF-κB regulatory factor c-IAP1 for degradation. / Csomos, Rebecca A.; Wright, Casey; Galbán, Stefanie; Oetjen, Karolyn A.; Duckett, Colin S.

In: Biochemical Journal, Vol. 420, No. 1, 15.05.2009, p. 83-91.

Research output: Contribution to journalArticle

Csomos, Rebecca A. ; Wright, Casey ; Galbán, Stefanie ; Oetjen, Karolyn A. ; Duckett, Colin S. / Two distinct signalling cascades target the NF-κB regulatory factor c-IAP1 for degradation. In: Biochemical Journal. 2009 ; Vol. 420, No. 1. pp. 83-91.
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