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Signal-specific co-activator domain requirements for Pit-1 activation

Author

Listed:
  • Lan Xu

    (Howard Hughes Medical Institute, University of California at San Diego
    Biomedical Sciences Graduate Program, University of California at San Diego)

  • Robert M. Lavinsky

    (Howard Hughes Medical Institute, University of California at San Diego
    University of California at San Diego)

  • Jeremy S. Dasen

    (Howard Hughes Medical Institute, University of California at San Diego
    Biomedical Sciences Graduate Program, University of California at San Diego)

  • Sarah E. Flynn

    (Howard Hughes Medical Institute, University of California at San Diego)

  • Eileen M. McInerney

    (Howard Hughes Medical Institute, University of California at San Diego)

  • Tina-Marie Mullen

    (Howard Hughes Medical Institute, University of California at San Diego
    Whittier Diabetes Program, University of California at San Diego
    Cellular and Molecular Medicine, and University of California at San Diego)

  • Thorsten Heinzel

    (Howard Hughes Medical Institute, University of California at San Diego)

  • Daniel Szeto

    (Howard Hughes Medical Institute, University of California at San Diego
    Biomedical Sciences Graduate Program, University of California at San Diego)

  • Edward Korzus

    (Howard Hughes Medical Institute, University of California at San Diego)

  • Riki Kurokawa

    (Cellular and Molecular Medicine, and University of California at San Diego
    University of California at San Diego)

  • Aneel K. Aggarwal

    (Mount Sinai School of Medicine)

  • David W. Rose

    (Whittier Diabetes Program, University of California at San Diego)

  • Christopher K. Glass

    (Cellular and Molecular Medicine, and University of California at San Diego
    University of California at San Diego)

  • Michael G. Rosenfeld

    (Howard Hughes Medical Institute, University of California at San Diego
    University of California at San Diego)

Abstract

POU-domain proteins, such as the pituitary-specific factor Pit-1, are members of the homeodomain family of proteins which are important in development and homeostasis, acting constitutively or in response to signal-transduction pathways to either repress or activate the expression of specific genes1. Here we show that whereas homeodomain-containing repressors such as Rpx2 seem to recruit only a co-repressor complex, the activity of Pit-1 (ref. 3) is determined by a regulated balance between a co-repressor complex that contains N-CoR/SMRT4,5, mSin3A/B6,7,8 and histone deacetylases6,7,8 and a co-activator complex that includes the CREB-binding protein (CBP)9 and p/CAF10. Activation of Pit-1 by cyclic AMP or growth factors depends on distinct amino- and carboxy-terminal domains of CBP, respectively. Furthermore, thehistone acetyltransferase functions of CBP11,12 or p/CAF10 are required for Pit-1 function that is stimulated by cyclic AMP or growth factors, respectively. These data show that there is a switch in specific requirements for histone acetyltransferases and CBP domains in mediating the effects of different signal-transduction pathways on specific DNA-bound transcription factors.

Suggested Citation

  • Lan Xu & Robert M. Lavinsky & Jeremy S. Dasen & Sarah E. Flynn & Eileen M. McInerney & Tina-Marie Mullen & Thorsten Heinzel & Daniel Szeto & Edward Korzus & Riki Kurokawa & Aneel K. Aggarwal & David W, 1998. "Signal-specific co-activator domain requirements for Pit-1 activation," Nature, Nature, vol. 395(6699), pages 301-306, September.
    • Handle: RePEc:nat:nature:v:395:y:1998:i:6699:d:10.1038_26270
    DOI: 10.1038/26270
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