TY - JOUR
T1 - Histone deacetylase 3 promotes RCAN1 stability and nuclear translocation
AU - Han, Kyung Ah
AU - Kang, Hye Seon
AU - Lee, Jee Won
AU - Yoo, Lang
AU - Im, Eunju
AU - Hong, Ahyoung
AU - Lee, Yun Ju
AU - Shin, Woo Hyun
AU - Chung, Kwang Chul
PY - 2014/8/21
Y1 - 2014/8/21
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0105416
DO - 10.1371/journal.pone.0105416
M3 - Article
C2 - 25144594
AN - SCOPUS:84928118048
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e105416
ER -