The role of calcium-binding proteins in the control of transcription: structure to function.
Transcriptional regulation is coupled with numerous intracellular signaling processes often mediated by second messengers. Now, growing evidence points to the importance of Ca(2+), one of the most versatile second messengers, in activating or inhibiting gene transcription through actions frequently mediated by members of the EF-hand superfamily of Ca(2+)-binding proteins. Calmodulin and calcineurin, representative members of this EF-hand superfamily, indirectly regulate transcription through phosphorylation/dephosphorylation of transcription factors in response to a Ca(2+) increase in the cell. Recently, a novel EF-hand Ca(2+)-binding protein called DREAM has been found to interact with regulatory sequences of DNA, thereby acting as a direct regulator of transcription. Finally, S100B, a dimeric EF-hand Ca(2+)-binding protein, interacts with the tumor suppressor p53 and controls its transcriptional activity. In light of the structural studies reported to date, this review provides an overview of the structural basis of EF-hand Ca(2+)-binding proteins linked with transcriptional regulation.
Ikura
Mitsuhiko
M
Division of Molecular and Structural Biology, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, 610 University Avenue, Room 7-707A, Toronto, Ontario, Canada M5G 2M9. mikura@uhnres.utoronto.ca
Osawa
Masanori
M
Ames
James B
JB
D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020832:EF Hand Motifs / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; D012097:Repressor Proteins