title: Re-evaluation of the role of calcium homeostasis endoplasmic reticulum protein (CHERP) in cellular calcium signaling.
abstract: Changes in cytoplasmic Ca(2+) concentration, resulting from activation of intracellular Ca(2+) channels within the endoplasmic reticulum, regulate several aspects of cellular growth and differentiation. Ca(2+) homeostasis endoplasmic reticulum protein (CHERP) is a ubiquitously expressed protein that has been proposed as a regulator of both major families of endoplasmic reticulum Ca(2+) channels, inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs), with resulting effects on mitotic cycling. However, the manner by which CHERP regulates intracellular Ca(2+) channels to impact cellular growth is unknown. Here, we challenge previous findings that CHERP acts as a direct cytoplasmic regulator of IP(3)Rs 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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Lin-Moshier
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sebastian
authors.forename: Leeann
authors.initials: L
authors.lastname: Higgins
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Sampson
authors.forename: Jane E
authors.initials: JE
authors.lastname: Hewitt
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Marchant
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C410225:CHERP protein, human; D004268:DNA-Binding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D009707:Nucleosomes; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D019837:Ryanodine Receptor Calcium Release Channel; C578532:U2SURP protein, human; D002118:Calcium