Ser-133 phosphorylation of the cAMP-responsive element-binding protein (CREB) is sufficient to induce cellular gene expression in response to cAMP, but additional promoter-bound factors are required for target gene activation by CREB in response to mitogen/stress signals. To compare the relative effects of different signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in living cells, we developed a fluorescence resonance energy transfer (FRET) assay. cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent manner by FRET analysis, but mitogen/stress signals were far less effective in stimulating complex formation even though they induced comparable levels of Ser-133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in promoting this interaction in the cytosol; the formation of CREB-CBP complexes in response to non-cAMP signals was specifically inhibited in the nucleus. Non-cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far Western blot assay, thereby supporting the presence of a distinct CREB-CBP antagonist. Our studies indicate that the relative effects of cAMP and mitogen/stress signals on CREB-CBP complex formation impart selectivity to gene activation through CREB phosphorylated at Ser-133.

Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB / B. M., Mayr; Canettieri, Gianluca; M. R., Montminy. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 98:19(2001), pp. 10936-10941. [10.1073/pnas.191152098]

Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB

CANETTIERI, Gianluca;
2001

Abstract

Ser-133 phosphorylation of the cAMP-responsive element-binding protein (CREB) is sufficient to induce cellular gene expression in response to cAMP, but additional promoter-bound factors are required for target gene activation by CREB in response to mitogen/stress signals. To compare the relative effects of different signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in living cells, we developed a fluorescence resonance energy transfer (FRET) assay. cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent manner by FRET analysis, but mitogen/stress signals were far less effective in stimulating complex formation even though they induced comparable levels of Ser-133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in promoting this interaction in the cytosol; the formation of CREB-CBP complexes in response to non-cAMP signals was specifically inhibited in the nucleus. Non-cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far Western blot assay, thereby supporting the presence of a distinct CREB-CBP antagonist. Our studies indicate that the relative effects of cAMP and mitogen/stress signals on CREB-CBP complex formation impart selectivity to gene activation through CREB phosphorylated at Ser-133.
2001
01 Pubblicazione su rivista::01a Articolo in rivista
Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB / B. M., Mayr; Canettieri, Gianluca; M. R., Montminy. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 98:19(2001), pp. 10936-10941. [10.1073/pnas.191152098]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/143214
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