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Endogenous IGFBP-3 mediates intrinsic apoptosis through modulation of Nur77 phosphorylation and nuclear export.

Endocrinology.. 2015-11;  156(11):4141-51
Agostini-Dreyer A, Jetzt AE, Stires H, Cohick WS. Department of Animal Sciences, Rutgers, The State University of New Jersey, 59 Dudley Road, New Brunswick, NJ 08901-8520.
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In nontransformed bovine mammary epithelial cells, the intrinsic apoptosis inducer anisomycin (ANS) induces IGFBP-3 expression and nuclear localization and knockdown of IGFBP-3 attenuates ANS-induced apoptosis. Others have shown in prostate cancer cells that exogenous IGFBP-3 induces apoptosis by facilitating nuclear export of the orphan nuclear receptor Nur77 and its binding partner, retinoid X receptor-α (RXRα). The goal of the present work was to determine whether endogenous IGFBP-3 plays a role in ANS-induced apoptosis by facilitating nuclear transport of Nur77 and/or RXRα in nontransformed cells. Knockdown of Nur77 with siRNA decreased ANS-induced cleavage of caspase-3 and -7 and their do... More