Site-specific phosphorylation of IκBα by a novel ubiquitination- dependent protein kinase activity

Z. J. Chen, L. Parent, T. Maniatis

Research output: Contribution to journalArticle

824 Citations (Scopus)

Abstract

Signal-induced activation of the transcription factor NF-κB requires specific phosphorylation of the inhibitor IκBα and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IκBα to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass ~700 kDa) that phosphorylates IκBα at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IκBα. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.

Original languageEnglish (US)
Pages (from-to)853-862
Number of pages10
JournalCell
Volume84
Issue number6
DOIs
StatePublished - 1996

Fingerprint

Phosphorylation
Ubiquitination
Protein Kinases
Phosphotransferases
Ubiquitin
Ubiquitin-Activating Enzymes
Proteolysis
Molecular mass
Corrosion inhibitors
Proteasome Endopeptidase Complex
Serine
Transcription Factors
Chemical activation
Degradation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Site-specific phosphorylation of IκBα by a novel ubiquitination- dependent protein kinase activity. / Chen, Z. J.; Parent, L.; Maniatis, T.

In: Cell, Vol. 84, No. 6, 1996, p. 853-862.

Research output: Contribution to journalArticle

@article{26f29afd7dd140fa864ff82eddc4aa68,
title = "Site-specific phosphorylation of IκBα by a novel ubiquitination- dependent protein kinase activity",
abstract = "Signal-induced activation of the transcription factor NF-κB requires specific phosphorylation of the inhibitor IκBα and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IκBα to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass ~700 kDa) that phosphorylates IκBα at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IκBα. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.",
author = "Chen, {Z. J.} and L. Parent and T. Maniatis",
year = "1996",
doi = "10.1016/S0092-8674(00)81064-8",
language = "English (US)",
volume = "84",
pages = "853--862",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Site-specific phosphorylation of IκBα by a novel ubiquitination- dependent protein kinase activity

AU - Chen, Z. J.

AU - Parent, L.

AU - Maniatis, T.

PY - 1996

Y1 - 1996

N2 - Signal-induced activation of the transcription factor NF-κB requires specific phosphorylation of the inhibitor IκBα and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IκBα to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass ~700 kDa) that phosphorylates IκBα at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IκBα. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.

AB - Signal-induced activation of the transcription factor NF-κB requires specific phosphorylation of the inhibitor IκBα and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IκBα to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass ~700 kDa) that phosphorylates IκBα at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IκBα. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.

UR - http://www.scopus.com/inward/record.url?scp=0030004897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030004897&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(00)81064-8

DO - 10.1016/S0092-8674(00)81064-8

M3 - Article

C2 - 8601309

AN - SCOPUS:0030004897

VL - 84

SP - 853

EP - 862

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -