Ca2+-dependent block of CREB-CBP transcription by repressor DREAM.
The calcium-binding protein DREAM binds specifically to DRE sites in the DNA and represses transcription of target genes. Derepression at DRE sites following PKA activation depends on a specific interaction between alphaCREM and DREAM. Two leucine-charged residue-rich domains (LCD) located in the kinase-inducible domain (KID) and in the leucine zipper of alphaCREM and two LCDs in DREAM participate in a two-site interaction that results in the loss of DREAM binding to DRE sites and derepression. Since the LCD motif located within the KID in CREM is also present in CREB, and maps in a region critical for the recruitment of CBP, we investigated whether DREAM may affect CRE-dependent transcription. Here we show that in the absence of Ca2+ DREAM binds to the LCD in the KID of CREB. As a result, DREAM impairs recruitment of CBP by phospho CREB and blocks CBP-mediated transactivation at CRE sites in a Ca2+-dependent manner. Thus, Ca2+-dependent interactions between DREAM and CREB represent a novel point of cross-talk between cAMP and Ca2+ signalling pathways in the nucleus.
Ledo
Fran
F
Centro Nacional de Biotecnología, C.S.I.C., Madrid, Spain.
Kremer
Leonor
L
Mellström
Britt
B
Naranjo
Jose R
JR
D001921:Brain / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins; D002460:Cell Line; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006801:Humans; D007668:Kidney; D051605:Kv Channel-Interacting Proteins; D016350:Leucine Zippers; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D002135:Calcium-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D002110:Caffeine; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium