Calcium/calmodulin inhibition of basic-helix-loop-helix transcription factor domains

The ubiquitous Ca(2+)-binding protein calmodulin (CaM) is a key protein in Ca2+ homeostasis and activation of eukaryotic cells. CaM is the molecular link between free Ca2+ in the cell and the inhibition, or activation, of numerous enzymes. Many nuclear functions are under Ca2+/CaM control, and some...

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Bibliographic Details
Published in:Nature (London) 1994-04, Vol.368 (6473), p.760-764
Main Authors: Corneliussen, Brit, Holm, Magnus, Waltersson, Yvonne, Onions, Jacqueline, Hallberg, Bengt, Thornell, Anders, Grundström, Thomas
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological and medical sciences
Calcium
Calcium - physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calmodulin - physiology
Cattle
Cell Line
Cellular biology
Cross-Linking Reagents - pharmacology
Deoxyribonucleic acid
DNA
DNA - metabolism
DNA-Binding Proteins - physiology
Fundamental and applied biological sciences. Psychology
Glutaral - pharmacology
Helix-Loop-Helix Motifs - physiology
Humans
Ionomycin - pharmacology
Mice
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Protein Binding
Proteins
Transcription Factors - physiology
Transcription, Genetic - physiology
Transcription. Transcription factor. Splicing. Rna processing
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Summary:The ubiquitous Ca(2+)-binding protein calmodulin (CaM) is a key protein in Ca2+ homeostasis and activation of eukaryotic cells. CaM is the molecular link between free Ca2+ in the cell and the inhibition, or activation, of numerous enzymes. Many nuclear functions are under Ca2+/CaM control, and some transcriptional activators are known to be Ca2+ modulated indirectly through Ca2+/CaM-dependent protein kinases. But Ca2+/CaM has not yet been found to directly modulate any transcription factor or other DNA-binding protein. Transcription factors of the basic-helix-loop-helix (bHLH) group are important regulators in numerous systems. Here we report that binding of Ca(2+)-loaded CaM to the bHLH domains of several bHLH proteins directly inhibits their DNA binding. Other bHLH proteins are either less sensitive or resistant. Ca2+ ionophore selectively inhibits transcriptional activation by Ca2+/CaM-sensitive bHLH proteins in vivo, implying that Ca2+ can directly influence transcription through differential CaM inhibition of bHLH domains.
ISSN:0028-0836
1476-4687
DOI:10.1038/368760a0