The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function

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The functionally conserved proteins CBP and p300 act in conjunction with other factors to activate transcription of DNA. A new factor, p/CIP, has been discovered that is present in the cell as a complex with CBP and is required for transcriptional activity of nuclear receptors and other CBP/p300-dependent transcription factors. The highly related nuclear-receptor co-activator protein NCoA-1 is also specifically required for ligand-dependent activation of genes by nuclear receptors. p/CIP, NCoA-1 and CBP all contain related leucine-rich charged helical interaction motifs that are required for receptor-specific mechanisms of gene activation, and allow the selective inhibition of distinct signal-transduction pathways.

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Figure 1: Characterization of a CBP-associated factor (p/CIP) and a related member of the NCoA family (NCoA-2).
Figure 2: Characterization of a CBP-associated factor (p/CIP) and a related member of the NCoA family (NCoA-2).
Figure 3: Biochemical analysis of p/CIP and NCoA factors.
Figure 4: Role of P/CIP in function of CBP-dependent transcription factors.
Figure 5: Role of NCoA-1 and NCoA-2 in nuclear receptor function.
Figure 6: Leucine charged domains (LCDs) of p/CIP/NCoA/CBP.
Figure 7: Leucine charged domains (LCDs) of p/CIP/NCoA/CBP.
Figure 8: Distinct helical motifs block transcriptional effects of specific signal transduction pathways.


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We thank N. Assa-Munt for discussions and help with computer analysis of protein structures; A. Aggarwal, T.-M. Mullen, J. Gemsh and C. Nelson for assistance; M. Parker for the RIP 140 cDNA clone, P. Myer for help in preparing the figures; and B. Stawiarski for help in preparing the manuscript. This work was supported by an American Diabetes Association career development award (to D.W.R.), by the National Cancer Institute of Canada (J.T.), by a Damon Runyon–Walter Winchell Foundation fellowship (J.I.) and by the Swedish Cancer Society (S.W.). M.G.R. is an investigator with the Howard Hughes Medical Institute. These studies were suppported by a US Army Breast Cancer Research Program and grants from the NIH to C.K.G. and M.G.R.

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Correspondence to David W. Rose or Michael G. Rosenfeld.

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