Protein-kinase-A-dependent activator in transcription factor CREB reveals new role for CREM repressors.
Hormonally induced increases in cyclic AMP levels induce phosphorylation of the transcription factor CREB at a serine residue at position 133 by protein kinase A (ref. 1), enhancing its ability to activate transcription without affecting its intracellular location or DNA-binding activity. This effect is dependent on a 60-amino-acid region of CREB that contains Ser133 and is termed the kinase-inducible domain (KID)2, which also occurs in the CREB-related CREM-alpha and -beta proteins, although these are transcriptional repressors. Here we show that the KID domain confers a cAMP-inducible increase on the activity of the Q2 activation domain from CREB and the acidic activation domains from the yeast proteins GAL4 and GCN4. Remarkably, it retains this ability even when attached to a separate polypeptide bound to an adjacent site in the promoter. KID may therefore be the first of a new class of conditional activators that work through other promoter-bound factors to stimulate gene expression in response to hormonal stimuli.
Brindle
P
P
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Linke
S
S
Montminy
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D005973:Glutamine; D051786:Cyclic AMP Response Element Modulator; D012694:Serine; D013004:Somatostatin; D004247:DNA; D011494:Protein Kinases