Publication Date:
2006-02-25
Description:
The transcription factor NF-kappaB modulates apoptotic responses induced by genotoxic stress. We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), associates with activated ataxia telangiectasia mutated (ATM) after the induction of DNA double-strand breaks. ATM phosphorylates serine-85 of NEMO to promote its ubiquitin-dependent nuclear export. ATM is also exported in a NEMO-dependent manner to the cytoplasm, where it associates with and causes the activation of IKK in a manner dependent on another IKK regulator, a protein rich in glutamate, leucine, lysine, and serine (ELKS). Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Zhao-Hui -- Shi, Yuling -- Tibbetts, Randal S -- Miyamoto, Shigeki -- R01-CA77474/CA/NCI NIH HHS/ -- R01-CA81065/CA/NCI NIH HHS/ -- R01-GM067868/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 24;311(5764):1141-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin-Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16497931" target="_blank"〉PubMed〈/a〉
Keywords:
Active Transport, Cell Nucleus
;
Adaptor Proteins, Signal Transducing/genetics/metabolism
;
Amino Acid Motifs
;
Ataxia Telangiectasia Mutated Proteins
;
Cell Cycle Proteins/*metabolism
;
Cell Line
;
Cell Nucleus/metabolism
;
Cytoplasm/metabolism
;
*DNA Damage
;
DNA-Binding Proteins/*metabolism
;
Humans
;
I-kappa B Kinase/*metabolism
;
I-kappa B Proteins/genetics/metabolism
;
NF-kappa B/metabolism
;
Nerve Tissue Proteins/genetics/metabolism
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/*metabolism
;
RNA Interference
;
Recombinant Fusion Proteins/metabolism
;
SUMO-1 Protein/metabolism
;
*Signal Transduction
;
Tumor Suppressor Proteins/*metabolism
;
Ubiquitin/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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