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

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Abstract

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.

References

  1. 1

    Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H. & Nakatani, Y. The transcriptional coactivator p300 and CBP are histone acetyltransferases. Cell 87, 953–960 (1996).

  2. 2

    Bannister, A. J. & Kouzarides, T. The CBP coactivator is a histone acetyltransferase. Nature 384, 641–643 (1996).

  3. 3

    Kamei, Y. et al. ACBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85, 1–12 (1996).

  4. 4

    Yao, T.-P., Ku, G., Zhou, N., Scully, R. & Livingston, D. M. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc. Natl Acad. Sci. USA 93, 10626–10631 (1996).

  5. 5

    Hanstein, B. et al. p300 is a component of an estrogen receptor coactivator complex. Proc. Natl Acad. Sci. USA 93, 11540–11545 (1996).

  6. 6

    Chakravarti, D. et al. Role of CBP/p300 in nuclear receptor signalling. Nature 383, 99–103 (1996).

  7. 7

    Kwok, R. P. et al. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370, 223–226 (1994).

  8. 8

    Arias, J. et al. Activation of cAMP and mitogen-responsive genes relies on a common nuclear factor. Nature 370, 226–229 (1994).

  9. 9

    Eckner, R., Yao, T.-P., Oldread, E. & Livingston, D. M. Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Genes Dev. 10, 2478–2490 (1996).

  10. 10

    Bhattacharya, S. et al. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-α. Nature 383, 344–347 (1996).

  11. 11

    Zhang, J. J. et al. Two contact regions between Stat1 and CBP/p300 in interferon γ signaling. Proc. Natl Acad. Sci. USA 93, 15092–15096 (1996).

  12. 12

    Horvai, A. E. et al. Nuclear integration of JAK/STAT and ras signaling by CBP and p300. Proc. Natl Acad. Sci. USA 94, 1074–1079 (1997).

  13. 13

    Chambon, P. The retinoid signaling pathway: molecular and genetic analyses. Semin. Cell Biol. 5, 115–125 (1994).

  14. 14

    Beato, M., Herrlich, P. & Schütz, G. Steroid hormone receptors: many actors in search of a plot. Cell 83, 851–857 (1995).

  15. 15

    Tsai, M. J. & O'Malley, B. W. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63, 451–486 (1994).

  16. 16

    Danielian, P. S., White, R., Lees, J. A. & Parker, M. G. Identification of a conserved region required for hormone-dependent transcriptional activation by steroid hormone receptors. EMBO J. 11, 1025–1033 (1992).

  17. 17

    Durand, B. et al. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity. EMBO J. 13, 5370–5380 (1994).

  18. 18

    Barettino, D., Vivanco Ruiz, M. M. & Stunnenberg, H. G. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor. EMBO J. 13, 3039–3049 (1994).

  19. 19

    Tone, Y., Collingwood, T. N., Adams, M. & Chatterjee, V. K. Functional analysis of a transactivation domain in the thyroid hormone beta receptor. J. Biol. Chem. 369, 31157–31161 (1994).

  20. 20

    Bourguet, W., Ruff, M., Chambon, P., Gronemeyer, H. & Moras, D. Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α. Nature 375, 377–382 (1995).

  21. 21

    Renaud, J.-P. et al. Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acid. Nature 378, 681–689 (1995).

  22. 22

    Wagner, R. L. et al. Astructural role for hormone in the thyroid hormone receptor. Nature 378, 690–696 (1995).

  23. 23

    Halachmi, S. et al. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science 264, 1455–1458 (1994).

  24. 24

    Cavailles, V. et al. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 14, 3741–3751 (1995).

  25. 25

    Kurokawa, R. et al. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature 377, 451–454 (1995).

  26. 26

    Fondell, J. D., Ge, H. & Roeder, R. G. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc. Natl Acad. Sci. USA 93, 8329–8338 (1996).

  27. 27

    Lee, J. W., Ryan, F., Swaffield, J. C., Johnston, S. A. & Moore, D. D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature 374, 91–94 (1995).

  28. 28

    Le Douarin, B. et al. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-ref in the oncogenic protein T18. EMBO J. 14, 2020–2033 (1995).

  29. 29

    Oñate, S. A., Tsai, S. Y., Tsai, M.-J. & O'Malley, B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270, 1354–1357 (1995).

  30. 30

    Cavailles, N., Dauvois, S., Danielian, P. S. & Parker, M. G. Interaction of proteins with transcriptionally active estrogen receptors. Proc. Natl Acad. Sci. USA 91, 10009–10013 (1994).

  31. 31

    Voegel, J. J., Heine, M. J. S., Zechel, C., Chambon, P. & Gronemeyer, H. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J. 15, 3667–3675 (1996).

  32. 32

    Hong, H., Kohli, K., Trivedi, A., Johnson, D. L. & Stallcup, M. R. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc. Natl Acad. Sci. USA 93, 4948–4952 (1996).

  33. 33

    Smith, C. L., Oñate, S. A., Tsai, M.-J. & O'Malley, B. W. CREB binding protein acta synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription. Proc. Natl Acad. Sci. USA 93, 8884–8888 (1996).

  34. 34

    Geourjon, C. & Deleage, G. SOPM: a self optimised prediction method for protein secondary structure prediction. Protein Eng. 7, 157–164 (1994).

  35. 35

    Dai, P. et al. CBP as a transcriptional coactivator of c-Myb. Genes Dev. 10, 528–540 (1996).

  36. 36

    Lee, J.-S. et al. Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300. Genes Dev. 9, 1188–1198 (1995).

  37. 37

    Oliner, J. D., Andresen, J. M., Hansen, S. K., Zhou, S. & Tjian, R. SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein. Genes Dev. 10, 2903–2911 (1996).

  38. 38

    Bisotto, S., Minorgan, S. & Rehfus, R. P. Identification and characterization of a novel transcriptional activation domain in the CREB-binding protein. J. Biol. Chem. 271, 17746–17750 (1996).

  39. 39

    Swope, D. L., Mueller, C. L. & Chrivia, J. C. CREB-binding protein activates transcription through multiple domains. J. Biol. Chem. 271, 28138–28145 (1996).

  40. 40

    Nakajima, T., Uchida, C., Anderson, S. F., Parvin, J. D. & Montminy, M. Analysis of a cAMP-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors. Genes Dev. 11, 738–747 (1997).

  41. 41

    Yang, X.-Y., Ogryzko, V. V., Nishikawa, J., Howard, B. H. & Nakatani, Y. Ap300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature 382, 319–324 (1996).

  42. 42

    Nakajima, T. et al. The signal-dependent coactivator CBP is a nuclear target for pp90 rsk. Cell 86, 465–474 (1996).

  43. 43

    Gyuris, J., Golemis, E., Chertkov, H. & Brent, R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75, 791–803 (1993).

  44. 44

    Ausubel, F. M. et al. Current Protocols in Molecular Biology (Greene, New York, 1994).

  45. 45

    Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1988).

  46. 46

    Laemmle, E. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685 (1970).

  47. 47

    Rose, D. W., McCabe, G., Feramisco, J. R. & Adler, M. Expression of c-fos and AP-1 activity in senescent human fibroblasts is not sufficient for DNA synthesis. J. Cell. Biol. 119, 1405–1411 (1992).

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Acknowledgements

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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