title: RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling.
abstract: Forced changes in the expression of regulator of calcineurin 1 (RCAN1) affects cell growth. This has been linked to the suppression of calcineurin-nuclear factor of activated T cells signaling by RCAN1. Here, we describe a novel role of RCAN1 isoform 4 in proper expression of Ras protein and its signaling. RCAN1 isoform 4 knockdown attenuated growth factor-induced extracellular signal-regulated kinase activation and cell growth; reduced Ras levels and its translation rate; and led to a reduction of eukaryotic initiation factor 4E in the initiation complex and a slight repression of global protein synthesis. Experiments utilizing activity-modified mutants of calcineurin A demonstrated that these effects were calcineurin-independent. Our findings reveal a previously unknown role of RCAN1-4 in protein synthesis, which may be relevant to cell growth.
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hong Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Cho
mesh_terms: D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002460:Cell Line; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C108612:RCAN1 protein, human; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases; D019703:Calcineurin; D018631:ras Proteins