Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biocel.2010.12.017
Title: Activation of a non-genomic Pim-1/Bad-Pser75 module is required for an efficient pro-survival effect of Bcl-xL induced by androgen in LNCaP cells
Authors: Kumar, J.K.
Ping, R.Y.S.
Teong, H.F.
Goh, S.
Clément, M.-V. 
Keywords: Bad
Bcl-xL
LY294002
Pim-1
Prostate cancer
Issue Date: Apr-2011
Citation: Kumar, J.K., Ping, R.Y.S., Teong, H.F., Goh, S., Clément, M.-V. (2011-04). Activation of a non-genomic Pim-1/Bad-Pser75 module is required for an efficient pro-survival effect of Bcl-xL induced by androgen in LNCaP cells. International Journal of Biochemistry and Cell Biology 43 (4) : 594-603. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biocel.2010.12.017
Abstract: The present report investigated the pathway(s) involved in the inhibition of apoptosis by the synthetic androgen, R1881 in serum-starved LNCaP cells exposed to the pi3K inhibitor, LY294002. R1881 blocked LY294002-induced apoptosis through the inhibition of Bak activation via an increase in Bcl-xL transcription and protein expression. In addition, R1881 treatment enhanced the stability of the Pim-1 kinase, resulting in the inhibition of the activation of the BH3-only protein Bad through its phosphorylation at ser75. Pharmacological inhibition of the Pim-1 kinase activity with quercetagetin, a highly selective Pim-1 inhibitor, prevented R1881-mediated increase in Bad phosphorylation and restored cell sensitivity to LY294002-induced apoptosis despite the increase in Bcl-xL expression. These results demonstrate for the first time that the inhibition of LY294002-induced apoptosis by androgen is a function of an androgen receptor-dependent genomic signaling pathway leading to an increase in Bcl-xL expression as well as a non-genomic, Pim-1-dependent, signaling pathway mediated via phosphorylation of Bad at ser75. © 2010 Elsevier Ltd. All rights reserved.
Source Title: International Journal of Biochemistry and Cell Biology
URI: http://scholarbank.nus.edu.sg/handle/10635/109155
ISSN: 13572725
DOI: 10.1016/j.biocel.2010.12.017
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