TY - JOUR
T1 - Re-evaluation of the role of Calcium Homeostasis Endoplasmic Reticulum Protein (CHERP) in cellular calcium signaling
AU - Lin-Moshier, Yaping
AU - Sebastian, Peter J.
AU - Higgins, LeeAnn
AU - Sampson, Natalie D.
AU - Hewitt, Jane E.
AU - Marchant, Jonathan S.
PY - 2013/1/4
Y1 - 2013/1/4
N2 - Changes in cytoplasmic Ca2+ concentration, resulting from activation of intracellular Ca2+ channels within the endoplasmic reticulum, regulate several aspects of cellular growth and differentiation. Ca2+ homeostasis endoplasmic reticulum protein (CHERP) is a ubiquitously expressed protein that has been proposed as a regulator of both major families of endoplasmic reticulum Ca2+ channels, inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), with resulting effects on mitotic cycling. However, the manner by which CHERP regulates intracellular Ca2+ channels to impact cellular growth is unknown. Here, we challenge previous findings that CHERP acts as a direct cytoplasmic regulator of IP3Rs and RyRs and propose that CHERP acts in the nucleus to impact cellular proliferation by regulating the function of the U2 snRNA spliceosomal complex. The previously reported effects of CHERP on cellular growth therefore are likely indirect effects of altered spliceosomal function, consistent with prior data showing that loss of function of U2 snRNP components can interfere with cell growth and induce cell cycle arrest.
AB - Changes in cytoplasmic Ca2+ concentration, resulting from activation of intracellular Ca2+ channels within the endoplasmic reticulum, regulate several aspects of cellular growth and differentiation. Ca2+ homeostasis endoplasmic reticulum protein (CHERP) is a ubiquitously expressed protein that has been proposed as a regulator of both major families of endoplasmic reticulum Ca2+ channels, inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), with resulting effects on mitotic cycling. However, the manner by which CHERP regulates intracellular Ca2+ channels to impact cellular growth is unknown. Here, we challenge previous findings that CHERP acts as a direct cytoplasmic regulator of IP3Rs and RyRs and propose that CHERP acts in the nucleus to impact cellular proliferation by regulating the function of the U2 snRNA spliceosomal complex. The previously reported effects of CHERP on cellular growth therefore are likely indirect effects of altered spliceosomal function, consistent with prior data showing that loss of function of U2 snRNP components can interfere with cell growth and induce cell cycle arrest.
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U2 - 10.1074/jbc.M112.405761
DO - 10.1074/jbc.M112.405761
M3 - Article
C2 - 23148228
AN - SCOPUS:84872057373
SN - 0021-9258
VL - 288
SP - 355
EP - 367
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -