Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway
- PMID: 7628694
- DOI: 10.1101/gad.9.13.1586
Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway
Abstract
The transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate signal transduction pathways that result in the phosphorylation and subsequent degradation of I kappa B alpha. At present, the link between phosphorylation of I kappa B alpha and its degradation is not understood. In this report we provide evidence that phosphorylation of serine residues 32 and 36 of I kappa B alpha targets the protein to the ubiquitin-proteasome pathway. I kappa B alpha is ubiquitinated in vivo and in vitro following phosphorylation, and mutations that abolish phosphorylation and degradation of I kappa B alpha in vivo prevent ubiquitination in vitro. Ubiquitinated I kappa B alpha remains associated with NF-kappa B, and the bound I kappa B alpha is degraded by the 26S proteasome. Thus, ubiquitination provides a mechanistic link between phosphorylation and degradation of I kappa B alpha.
Similar articles
-
Control of IkappaBalpha proteolysis by the ubiquitin-proteasome pathway.Biochimie. 2001 Mar-Apr;83(3-4):351-6. doi: 10.1016/s0300-9084(01)01237-8. Biochimie. 2001. PMID: 11295496 Review.
-
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.Annu Rev Immunol. 2000;18:621-63. doi: 10.1146/annurev.immunol.18.1.621. Annu Rev Immunol. 2000. PMID: 10837071 Review.
-
Signal-induced degradation of I(kappa)B(alpha): association with NF-kappaB and the PEST sequence in I(kappa)B(alpha) are not required.Mol Cell Biol. 1996 Nov;16(11):6037-45. doi: 10.1128/MCB.16.11.6037. Mol Cell Biol. 1996. PMID: 8887633 Free PMC article.
-
Role of IkappaBalpha ubiquitination in signal-induced activation of NFkappaB in vivo.J Biol Chem. 1996 Mar 29;271(13):7844-50. doi: 10.1074/jbc.271.13.7844. J Biol Chem. 1996. PMID: 8631829
-
Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway.Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10599-603. doi: 10.1073/pnas.92.23.10599. Proc Natl Acad Sci U S A. 1995. PMID: 7479848 Free PMC article.
Cited by
-
Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue.Front Immunol. 2024 Apr 4;15:1381227. doi: 10.3389/fimmu.2024.1381227. eCollection 2024. Front Immunol. 2024. PMID: 38638434 Free PMC article. Review.
-
The role of proteasomes in tumorigenesis.Genes Dis. 2023 Aug 6;11(4):101070. doi: 10.1016/j.gendis.2023.06.037. eCollection 2024 Jul. Genes Dis. 2023. PMID: 38523673 Free PMC article. Review.
-
The Use of Soy Isoflavones in the Treatment of Prostate Cancer: A Focus on the Cellular Effects.Nutrients. 2023 Nov 21;15(23):4856. doi: 10.3390/nu15234856. Nutrients. 2023. PMID: 38068715 Free PMC article. Review.
-
CYLD in health and disease.Dis Model Mech. 2023 Jun 1;16(6):dmm050093. doi: 10.1242/dmm.050093. Epub 2023 Jun 30. Dis Model Mech. 2023. PMID: 37387450 Free PMC article. Review.
-
An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes.iScience. 2023 Feb 26;26(5):106276. doi: 10.1016/j.isci.2023.106276. eCollection 2023 May 19. iScience. 2023. PMID: 37168555 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases