Identification and characterization of an IkappaB kinase - PubMed (original) (raw)
Identification and characterization of an IkappaB kinase
C H Régnier et al. Cell. 1997.
Free article
Abstract
Activation of the transcription factor NF-kappaB by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-kappaB-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappaB-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappaB activation. CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both serine 32 and serine 36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway. This phosphorylation of IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappaB activation.
Similar articles
- IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK.
Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV. Woronicz JD, et al. Science. 1997 Oct 31;278(5339):866-9. doi: 10.1126/science.278.5339.866. Science. 1997. PMID: 9346485 - All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex.
Heilker R, Freuler F, Pulfer R, Di Padova F, Eder J. Heilker R, et al. Eur J Biochem. 1999 Jan;259(1-2):253-61. doi: 10.1046/j.1432-1327.1999.00028.x. Eur J Biochem. 1999. PMID: 9914500 - NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase.
Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. Ozes ON, et al. Nature. 1999 Sep 2;401(6748):82-5. doi: 10.1038/43466. Nature. 1999. PMID: 10485710 - How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex.
Karin M. Karin M. Oncogene. 1999 Nov 22;18(49):6867-74. doi: 10.1038/sj.onc.1203219. Oncogene. 1999. PMID: 10602462 Review. - Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Karin M, Ben-Neriah Y. Karin M, et al. Annu Rev Immunol. 2000;18:621-63. doi: 10.1146/annurev.immunol.18.1.621. Annu Rev Immunol. 2000. PMID: 10837071 Review.
Cited by
- SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.
Zhao W, Breese E, Bowers A, Hoggatt J, Pelus LM, Broxmeyer HE, Goebl M, Harrington MA. Zhao W, et al. PLoS One. 2013 Apr 22;8(4):e61123. doi: 10.1371/journal.pone.0061123. Print 2013. PLoS One. 2013. PMID: 23630580 Free PMC article. - Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes.
Sato T, Kotake D, Hiratsuka M, Hirasawa N. Sato T, et al. PLoS One. 2013;8(3):e59702. doi: 10.1371/journal.pone.0059702. Epub 2013 Mar 26. PLoS One. 2013. PMID: 23555753 Free PMC article. - Atypical IκB proteins - nuclear modulators of NF-κB signaling.
Schuster M, Annemann M, Plaza-Sirvent C, Schmitz I. Schuster M, et al. Cell Commun Signal. 2013 Apr 11;11(1):23. doi: 10.1186/1478-811X-11-23. Cell Commun Signal. 2013. PMID: 23578005 Free PMC article. - Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1(Ser376) in human articular chondrocytes.
Haseeb A, Chen D, Haqqi TM. Haseeb A, et al. Rheumatology (Oxford). 2013 Jun;52(6):998-1008. doi: 10.1093/rheumatology/kes363. Epub 2013 Feb 7. Rheumatology (Oxford). 2013. PMID: 23392593 Free PMC article. - Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B.
Jeay S, Pianetti S, Kagan HM, Sonenshein GE. Jeay S, et al. Mol Cell Biol. 2003 Apr;23(7):2251-63. doi: 10.1128/MCB.23.7.2251-2263.2003. Mol Cell Biol. 2003. PMID: 12640111 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous