Transcriptional activator CBP

The interaction of NF-kB with IkB provides a wealth of examples of several different kinds of order-disorder processes. This work was started in our lab as a collaboration with Dr. E.A. Komives at the University of California, San Diego. Nuclear factor-kappaB (NF-kB) is a dimeric transcription factor widely employed for the transcription of stress-response genes, as it binds to kB upstream enhancer DNA sequences, where it recruits the transcriptional activator CBP. In an unstressed cell, the majority of the NF-kB resides in the cytoplasm, in complex with the inhibitor of NF-kB (IkB). Response to stress involves phosphorylation and ubiquitination of IkB and its subsequent degradation by the proteasome. The free NF-kB is transported to the nucleus, where it binds to the kB enhancer sequences and mediates the transcription of genes that include that of IkB, which acts subsequently to remove NF-kB from the DNA and return it to the cytoplasm as the NF-kB-IkB complex. 

The participation of the different cofactors that form part of the transcription machinery is not homogeneous. Some, like pl60, can interact with both transcription activator domains of the receptor, TAF1 and TAF2, even though they utilize different pi60 domains. Others, like CBP/p300, do not enter into... 

One mechanism by which CBP and p300 could contribute to neuronal survival is through the transcription factor CREB (cAMP response element binding protein). Normally, activated CBP binds to CREB and acetylates the latter at three putative acetylation sites within its activation domain (Lu et al, 2003). It has been proposed... 

It is noteworthy that the CBP/p300 proteins are present in limited quantities thus creating a competition between transcription factors. CBP sequestration or CBP level drop, while inducing specific gene downregulation, could also represent a way to allow specific re-activation of a given gene. HDACi treatment may worsen this problem. 

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