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pISSN 1226-4512 eISSN 2093-3827


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Original Article

Korean J Physiol Pharmacol 2009; 13(6): 483-489

Published online December 30, 2009

Copyright © Korean J Physiol Pharmacol.

Knockdown of RCAN1.4 Increases Susceptibility to FAS-mediated and DNA-damage-induced Apoptosis by Upregulation of p53 Expression

Young Sun Kim1, Hong Joon Lee1, Chorong Jang1, Ho-Shik Kim2,3, and Young-Jin Cho1,3

Departments of 1Pharmacology, 2Biochemistry, and 3Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea


Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.

Keywords: RCAN1, Apoptosis, p53, Bax, HDM2