C-mip interacts physically with RelA and inhibits nuclear factor kappa B activity.
The fine regulation of NF-kappaB activity is crucial for both resting and stimulated cells and relies on complex balance between multiple activators and inhibitors. We report here that c-mip, a recently identified pleckstrin homology (PH) and leucine-rich repeat (LRR)-domain-containing protein, inactivates GSKbeta and interacts with RelA, a key member of the NF-kappaB family. We show that c-mip inhibits the degradation of I-kappaBalpha and impedes the dissociation of the NF-kappaB/I-kappaBalpha complexes. C-mip acts downstream signaling of classical NF-kappaB pathway and may represent one of the missing links in the control of NF-kappaB activity.
Kamal
Maud
M
INSERM, U 841, Créteil 94010, France; Institut Mondor de Recherche Biomédicale (IMRB), Département "génétique", Equipe "21", Créteil, F-94010, France.
Valanciute
Asta
A
Dahan
Karine
K
Ory
Virginie
V
Pawlak
Andre
A
Lang
P
P
Guellaen
Georges
G
Sahali
Djillali
D
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000276:immunology* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D051996:Transcription Factor RelA / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C540426:CMIP protein, human; D002352:Carrier Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3