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RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling

RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling

Febs Letters 583(15): 2557-2564

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.

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Accession: 055333730

Download citation: RISBibTeXText

PMID: 19619541

DOI: 10.1016/j.febslet.2009.07.023

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