Identification and characterization of an IkappaB kinase.

Abstract:

:Activation of the transcription factor NF-kappaB by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-kappaB-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappaB-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappaB activation. CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both serine 32 and serine 36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway. This phosphorylation of IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappaB activation.

journal_name

Cell

journal_title

Cell

authors

Régnier CH,Song HY,Gao X,Goeddel DV,Cao Z,Rothe M

doi

10.1016/s0092-8674(00)80344-x

subject

Has Abstract

pub_date

1997-07-25 00:00:00

pages

373-83

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)80344-X

journal_volume

90

pub_type

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