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CBP-independent activation of CREM and CREB by the LIM-only protein ACT

Nature volume 398, pages 165–169 (1999)Cite this article

Abstract

Transcriptional activation by CREB and CREM requires phosphorylation of a serine residue within the activation domain (Ser 133 in CREB; Ser 117 in CREM) which as a result interacts with the coactivator CBP1,2. The activator CREM is highly expressed in male germ cells and is required for post-meiotic gene expression2,3,4. Using a two-hybrid screen, we have isolated a testis-derived complementary DNA encoding a protein that we term ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM. ACT is expressed coordinately with CREM in a tissue- and developmentally regulated manner. It strongly stimulates CREM transcriptional activity in yeast and mammalian cells and contains an intrinsic activation function. As ACT bypasses the classical requirements for activation, namely phosphorylation of Ser 117 and interaction with CBP, it represents a new route for transcriptional activation by CREM and CREB. ACT may define a previously undiscovered class of tissue-specific coactivators whose function could be specific for distinct cellular differentiation programmes.

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Figure 1: Isolation of a CREM coactivator in testis by yeast two-hybrid assay.
Figure 2: Analysis of ACT expression.
Figure 3: ACT associates with CREM.
Figure 4: ACT is a coactivator.
Figure 5: CREM Ser 117 phosphorylation is not required for ACT function.

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Acknowledgements

We thank L. Monaco, N. S. Foulkes, A. R. Means, K. E. Bernstein, T. Kouzarides, K.Tamai, E. Heitz and all the members of the Sassone-Corsi laboratory for help, reagents and discussions. G. M. F. and D. D. C. were supported by post-doctoral fellowships from the European Community. This work was supported by grants from Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire Régional, Fondation de la Recherche Médicale, Université Louis Pasteur and Association pour la Recherche sur le Cancer.

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  1. Gian Maria Fimia and Dario De Cesare: These authors contributed equally to the work

Authors and Affiliations

  1. Institut de Gntique et de Biologie Molculaire et Cellulaire, CNRS-INSERM-ULP, B. P. 163, Illkirch, 67404, Strasbourg, France

    Paolo Sassone-Corsi

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  1. Gian Maria Fimia
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Correspondence to Paolo Sassone-Corsi.

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Fimia, G., Cesare, D. & Sassone-Corsi, P. CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 398, 165–169 (1999). https://doi.org/10.1038/18237

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