RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling.
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.
Lee
Hong Joon
HJ
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Kim
Young Sun
YS
Sato
Yasufumi
Y
Cho
Young-Jin
YJ
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*
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