期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：1
页码：307-312
DOI：10.1073/pnas.0136791100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The {beta} subunits of voltage-gated Ca2+ 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 Ca2+-channel 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 2/heterochromatin protein 1{gamma} (CHCB2/HP1{gamma}), 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 2/heterochromatin protein 1{gamma}. The {beta}4c subunit is therefore a multifunctional protein that not only constitutes a portion of the Ca2+ channel but also regulates gene transcription.
