Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s).
Calsenilin/potassium channel-interacting protein (KChIP)3/ downstream regulatory element sequence antagonist modulator (DREAM) is a neuronal calcium-binding protein that has been shown to have multiple functions in the cell, including the regulation of presenilin processing, repression of transcription and modulation of A-type potassium channels. To gain a better understanding of the precise ... role of calsenilin in specific cellular compartments, an interactor hunt for proteins that bind to the N-terminal domain of calsenilin was carried out. Using a yeast two-hybrid system and co-immunoprecipitation studies, we have identified the transcriptional co-repressor C-terminal binding protein (CtBP)2 as an interactor for calsenilin and have shown that the two proteins can interact in vivo. In co-immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog. Our data also showed a calsenilin-dependent increase in c-fos protein levels in CtBP knockout fibroblasts, suggesting that CtBP may modulate the transcriptional repression of c-fos by calsenilin. Furthermore, the finding that histone deacetylase protein and activity were associated with the calsenilin-CtBP immunocomplex suggests a mechanism by which calsenilin-CtBP may act to repress transcription. Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interact in vivo.
Mesh Terms:
Alcohol Oxidoreductases, Animals, Blotting, Western, Calcium-Binding Proteins, Cell Line, Tumor, Cerebellum, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Fibroblasts, Histone Deacetylases, Immunoprecipitation, Kv Channel-Interacting Proteins, Mice, Mice, Knockout, Microscopy, Confocal, Nerve Tissue Proteins, Neuronal Calcium-Sensor Proteins, Neuropeptides, Phosphoproteins, Proto-Oncogene Proteins c-fos, Repressor Proteins, Saccharomyces cerevisiae, Synaptic Vesicles, Transcription, Genetic, Transfection
Alcohol Oxidoreductases, Animals, Blotting, Western, Calcium-Binding Proteins, Cell Line, Tumor, Cerebellum, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Fibroblasts, Histone Deacetylases, Immunoprecipitation, Kv Channel-Interacting Proteins, Mice, Mice, Knockout, Microscopy, Confocal, Nerve Tissue Proteins, Neuronal Calcium-Sensor Proteins, Neuropeptides, Phosphoproteins, Proto-Oncogene Proteins c-fos, Repressor Proteins, Saccharomyces cerevisiae, Synaptic Vesicles, Transcription, Genetic, Transfection
J. Neurochem.
Date: Aug. 01, 2006
PubMed ID: 16787403
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