Cited by 221NF-κB Signaling PathwaysGenomics and Chromatin DynamicsSignaling Pathways in Disease

SMRT Derepression by the IκB Kinase α

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Hoberg, Jamie E., Yeung, Fan, Mayo, Marty W.·2004·Molecular Cell

Abstract

Understanding how signaling cascades stimulate chromatin-remodeling events through derepression is one of the foremost questions in the transcription field. Here, we demonstrate that NF-kappaB transcription requires IKKalpha to phosphorylate SMRT on chromatin, stimulating the exchange of corepressor for coactivator complexes. IKKalpha-induced phosphorylation coincides with a loss of chromatin-associated SMRT and HDAC3 and with nuclear export of the SMRT corepressor, events required for expression of the NF-kappaB-regulated cIAP-2 and IL-8 genes. Although SMRT derepression corresponds with the recruitment of TBL1/TBLR1, this complex alone is insufficient to relieve repression. Using a nonphosphorylatable SMRT protein, we demonstrate that IKKalpha-induced phosphorylation is required to recruit 14-3-3epsilon and Ubc5 for SMRT derepression. Failure of IKKalpha to stimulate the removal of SMRT from chromatin inhibits the recruitment of NF-kappaB to promoters, blocking transcription and sensitizing cells to apoptosis. Our work provides evidence that IKKalpha orchestrates SMRT derepression, a prerequisite for NF-kappaB transcription and survival.

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Crossref · 10.1016/j.molcel.2004.10.010

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Authors
Hoberg, J. E., Yeung, F., & Mayo, M. W.
Affiliations
University of Virginia (US)
Corresponding author
Mayo, Marty W.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2004-10
Volume
16
Issue
2
Pages
245-255
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2603306439
Cited by
220
References
46
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 10 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 20 · 2012: 18
FWCI
8.22
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k01ca078595-04)
  • National Cancer Institute (CA78595, R01CA104397, R01CA095644, CA104397, CA095644, CA110552, F32CA110552)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
SMRT, IKKα, NF-κB transcription, coactivator complexes, HDAC3, 14-3-3ε, cIAP2, interleukin-8, apoptosis, chromatin remodeling
MeSH terms
Cell Nucleus, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Humans, Laminin, Phosphorylation, Repressor Proteins, Serine, Transcription, Genetic, NF-kappa B, Protein Serine-Threonine Kinases, Protein Transport, I-kappa B Kinase, Nuclear Receptor Co-Repressor 2

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