DREAM-alphaCREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription.
Protein kinase A-dependent derepression of the human prodynorphin gene is regulated by the differential occupancy of the Dyn downstream regulatory element (DRE) site. Here, we show that a direct protein-protein interaction between DREAM and the CREM repressor isoform, alphaCREM, prevents binding of DREAM to the DRE and suggests a mechanism for cyclic AMP-dependent derepression of the prodynorphin gene in human neuroblastoma cells. Phosphorylation in the kinase-inducible domain of alphaCREM is not required for the interaction, but phospho-alphaCREM shows higher affinity for DREAM. The interaction with alphaCREM is independent of the Ca(2+)-binding properties of DREAM and is governed by leucine-charged residue-rich domains located in both alphaCREM and DREAM. Thus, our results propose a new mechanism for DREAM-mediated derepression that can operate independently of changes in nuclear Ca(2+).
Ledo
F
F
Departamento Biología Molecular y Celular, Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Carrión
A M
AM
Link
W A
WA
Mellström
B
B
Naranjo
J R
JR
D020816:Amino Acid Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; 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 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004745:Enkephalins / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005809:Genes, Regulator / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma; D010766:Phosphorylation; D011498:Protein Precursors / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014162:Transfection; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004745:Enkephalins; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D005576:Colforsin; C033660:preproenkephalin; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium