Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II

D. Wang, S. D. Westerheide, J. L. Hanson, Jr Baldwin A.S.

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Nuclear factor κB (NF-κB)/Rel transcription factors are key regulators of a variety of genes involved in immune and inflammatory responses, growth, differentiation, apoptosis, and development. In unstimulated cells, NF-κB/Rel proteins are sequestered in the cytoplasm by IκB inhibitor proteins. Many extracellular stimuli, such as tumor necrosis factor α (TNFα), cause rapid phosphorylation of IκB at N-terminal serine residues leading to ubiquitination and degradation of the inhibitor. Subsequently, NF-κB proteins translocate to the nucleus and activate gene expression through κB response elements. TNFα, as well as certain other stimuli, also induces the phosphorylation of the NF-κB proteins. Previously, we have shown that TNFα induces RelA/p65 phosphorylation at serine 529 and that this inducible phosphorylation increases NF-κB transcriptional activity on an exogenously supplied reporter (1). In this report, we demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFα-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IκBα and p65 inhibits p65 phosphorylation by CKII and that degradation of IκBα allows CKII to phosphorylate p65 to increase NF-κB transactivation potential. These data may explain the ability of CKII to modulate cell growth and demonstrate a mechanism whereby CKII can function in an inducible manner.

Original languageEnglish (US)
Pages (from-to)32592-32597
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number42
DOIs
StatePublished - Oct 20 2000

Fingerprint

Casein Kinase II
Phosphorylation
Tumor Necrosis Factor-alpha
Serine
Proteins
Degradation
Ubiquitination
Cell growth
Response Elements
Corrosion inhibitors
Growth
Gene expression
Transcriptional Activation
Cytoplasm
Transcription Factors
Genes
Association reactions
Apoptosis
Gene Expression

Cite this

Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. / Wang, D.; Westerheide, S. D.; Hanson, J. L.; Baldwin A.S., Jr.

In: Journal of Biological Chemistry, Vol. 275, No. 42, 20.10.2000, p. 32592-32597.

Research output: Contribution to journalArticle

Wang, D. ; Westerheide, S. D. ; Hanson, J. L. ; Baldwin A.S., Jr. / Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 42. pp. 32592-32597.
@article{3708b6db20704c1abe359d535d0df014,
title = "Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II",
abstract = "Nuclear factor κB (NF-κB)/Rel transcription factors are key regulators of a variety of genes involved in immune and inflammatory responses, growth, differentiation, apoptosis, and development. In unstimulated cells, NF-κB/Rel proteins are sequestered in the cytoplasm by IκB inhibitor proteins. Many extracellular stimuli, such as tumor necrosis factor α (TNFα), cause rapid phosphorylation of IκB at N-terminal serine residues leading to ubiquitination and degradation of the inhibitor. Subsequently, NF-κB proteins translocate to the nucleus and activate gene expression through κB response elements. TNFα, as well as certain other stimuli, also induces the phosphorylation of the NF-κB proteins. Previously, we have shown that TNFα induces RelA/p65 phosphorylation at serine 529 and that this inducible phosphorylation increases NF-κB transcriptional activity on an exogenously supplied reporter (1). In this report, we demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFα-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IκBα and p65 inhibits p65 phosphorylation by CKII and that degradation of IκBα allows CKII to phosphorylate p65 to increase NF-κB transactivation potential. These data may explain the ability of CKII to modulate cell growth and demonstrate a mechanism whereby CKII can function in an inducible manner.",
author = "D. Wang and Westerheide, {S. D.} and Hanson, {J. L.} and {Baldwin A.S.}, Jr",
year = "2000",
month = "10",
day = "20",
doi = "10.1074/jbc.M001358200",
language = "English (US)",
volume = "275",
pages = "32592--32597",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "42",

}

TY - JOUR

T1 - Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II

AU - Wang, D.

AU - Westerheide, S. D.

AU - Hanson, J. L.

AU - Baldwin A.S., Jr

PY - 2000/10/20

Y1 - 2000/10/20

N2 - Nuclear factor κB (NF-κB)/Rel transcription factors are key regulators of a variety of genes involved in immune and inflammatory responses, growth, differentiation, apoptosis, and development. In unstimulated cells, NF-κB/Rel proteins are sequestered in the cytoplasm by IκB inhibitor proteins. Many extracellular stimuli, such as tumor necrosis factor α (TNFα), cause rapid phosphorylation of IκB at N-terminal serine residues leading to ubiquitination and degradation of the inhibitor. Subsequently, NF-κB proteins translocate to the nucleus and activate gene expression through κB response elements. TNFα, as well as certain other stimuli, also induces the phosphorylation of the NF-κB proteins. Previously, we have shown that TNFα induces RelA/p65 phosphorylation at serine 529 and that this inducible phosphorylation increases NF-κB transcriptional activity on an exogenously supplied reporter (1). In this report, we demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFα-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IκBα and p65 inhibits p65 phosphorylation by CKII and that degradation of IκBα allows CKII to phosphorylate p65 to increase NF-κB transactivation potential. These data may explain the ability of CKII to modulate cell growth and demonstrate a mechanism whereby CKII can function in an inducible manner.

AB - Nuclear factor κB (NF-κB)/Rel transcription factors are key regulators of a variety of genes involved in immune and inflammatory responses, growth, differentiation, apoptosis, and development. In unstimulated cells, NF-κB/Rel proteins are sequestered in the cytoplasm by IκB inhibitor proteins. Many extracellular stimuli, such as tumor necrosis factor α (TNFα), cause rapid phosphorylation of IκB at N-terminal serine residues leading to ubiquitination and degradation of the inhibitor. Subsequently, NF-κB proteins translocate to the nucleus and activate gene expression through κB response elements. TNFα, as well as certain other stimuli, also induces the phosphorylation of the NF-κB proteins. Previously, we have shown that TNFα induces RelA/p65 phosphorylation at serine 529 and that this inducible phosphorylation increases NF-κB transcriptional activity on an exogenously supplied reporter (1). In this report, we demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFα-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IκBα and p65 inhibits p65 phosphorylation by CKII and that degradation of IκBα allows CKII to phosphorylate p65 to increase NF-κB transactivation potential. These data may explain the ability of CKII to modulate cell growth and demonstrate a mechanism whereby CKII can function in an inducible manner.

UR - http://www.scopus.com/inward/record.url?scp=0034693133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034693133&partnerID=8YFLogxK

U2 - 10.1074/jbc.M001358200

DO - 10.1074/jbc.M001358200

M3 - Article

C2 - 10938077

AN - SCOPUS:0034693133

VL - 275

SP - 32592

EP - 32597

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 42

ER -