NDLI: Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the $Ca^{2+}-channel$ $β_{4}$ subunit

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Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the $Ca^{2+}-channel$ $β_{4}$ subunit

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Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the $Ca^{2+}-channel$ $β_{4}$ subunit

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hibino, H. Lesage, F. Hudspeth, A. J. Rousset, M. Pironkova, R. Onwumere, O. Charnet, P.
Description	Author Affiliation: Hibino H ( The Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.);
Abstract	The beta subunits of voltage-gated Ca(2+) channels are known to be regulators of the channels' gating properties. Here we report a striking additional function of a beta subunit. Screening of chicken cochlear and brain cDNA libraries identified beta(4c), a short splice variant of the beta(4) subunit. Although beta(4c) occurs together with the longer isoforms beta(4a) or beta(4b) in the brain, eye, heart, and lung, the cochlea expresses exclusively beta(4c). The association of beta(4c) with the Ca(2+)-channel alpha(1) subunit has slight but significant effects on the kinetics of channel activation and inactivation. Yeast two-hybrid and biochemical assays revealed that beta(4c) interacts directly with the chromo shadow domain of chromobox protein 2heterochromatin protein 1gamma (CHCB2HP1gamma), a nuclear protein involved in gene silencing and transcriptional regulation. Coexpression of this protein specifically recruits beta(4c) to the nuclei of mammalian cells. Furthermore, beta(4c) but not beta(4a) dramatically attenuates the gene-silencing activity of chromobox protein 2heterochromatin protein 1gamma. The beta(4c) subunit is therefore a multifunctional protein that not only constitutes a portion of the Ca(2+) channel but also regulates gene transcription.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Physiology Calcium Channels Genetics Cochlea Gene Silencing Genetic Variation Nuclear Proteins Metabolism Alternative Splicing Animals COS Cells Cercopithecus Aethiops Cloning, Molecular DNA Primers Gene Library Hair Cells, Auditory Membrane Potentials Oocytes Protein Subunits Recombinant Fusion Proteins Reverse Transcriptase Polymerase Chain Reaction Transfection Xenopus Laevis Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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