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First published online August 24, 2006
doi: 10.1242/10.1242/jcs.03086
Research Article |
B
complexes requires 14-3-3 proteins
Centre Oncologia Molecular, IDIBELL-Institut de Recerca Oncologica, Gran Via km 2.7, Hospitalet, Barcelona 08907, Spain
* Authors for correspondence (e-mail: abigas{at}iro.es; llespinosa{at}iro.es)
Accepted 6 June 2006
I
B are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NF
B activation to terminate the signal. We now show that 14-3-3 proteins regulate the NF
B signaling pathway by physically interacting with p65 and I
B
proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of I
B
in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or I
B
results in a predominantly nuclear distribution of both proteins. TNF
treatment promotes recruitment of 14-3-3 and I
B
to NF
B-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-I
B
complexes and the constitutive association of p65 with the chromatin. In this situation, NF
B-dependent genes become unresponsive to TNF
stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of I
B
-p65 complexes and are required for the appropriate regulation of NF
B signaling.
Key words: NF
B, I
B
, 14-3-3, Nuclear export, TNF
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B - capped by 14-3-3
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