title: Histone deacetylase 3 promotes RCAN1 stability and nuclear translocation.
abstract: Regulator of calcineurin 1 (RCAN1; also referred as DSCR1 or MCIP1) is located in close proximity to a Down syndrome critical region of human chromosome 21. Although RCAN1 is an endogenous inhibitor of calcineurin signaling that controls lymphocyte activation, apoptosis, heart development, skeletal muscle differentiation, and cardiac function, it is not yet clear whether RCAN1 might be involved in other cellular activities. In this study, we explored the extra-functional roles of RCAN1 by searching for novel RCAN1-binding partners. Using a yeast two-hybrid assay, we found that RCAN1 (RCAN1-1S) interacts with histone deacetylase 3 (HDAC3) in mammalian cells. We also demonstrate that HDAC3 deacetylates RCAN1. In addition, HDAC3 increases RCAN1 protein stability by inhibiting its poly-ubiquitination. Furthermore, HDAC3 promotes RCAN1 nuclear translocation. These data suggest that HDAC3, a new binding regulator of RCAN1, affects the protein stability and intracellular localization of RCAN1.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Han
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Jee Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Lang
authors.initials: L
authors.lastname: Yoo
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Im
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Ahyoung
authors.initials: A
authors.lastname: Hong
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Yun Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Shin
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D004268:DNA-Binding Proteins; D015870:Gene Expression; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D013379:Substrate Specificity; D054875:Ubiquitination; D000099186:Histone Deacetylase 3
chemical_list: D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D000099186:Histone Deacetylase 3; C108612:RCAN1 protein, human