Endogenous IGFBP-3 Mediates Intrinsic Apoptosis Through Modulation of Nur77 Phosphorylation and Nuclear Export

Endocrinology
Allyson Agostini-DreyerW S Cohick

Abstract

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 downstream target, PARP, indicating a role for Nur77 in ANS-induced apoptosis. In cells transfected with IGFBP-3, IGFBP-3 associated with RXRα but not Nur77 under basal conditions, however, IGFBP-3 co-precipitated with phosphorylated forms of both proteins in ANS-treated cells. Indirect immunofluorescence and cell fractionation techniques showed that ANS induced phosphorylation and transport of Nur77 from the nucleus to the cytoplasm and these effects were attenuated by knockdown of IGFBP-3. These data suggest that endogenous IGFBP-3 plays a...Continue Reading

References

Jun 26, 1999·The Journal of Biological Chemistry·S Adam-StitahC Rochette-Egly
May 16, 2000·The Journal of Biological Chemistry·L J SchedlichR C Baxter
Jul 6, 2000·Nature Cell Biology·Y KatagiriG Guroff
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y PekarskyC M Croce
Jul 5, 2001·The Journal of Biological Chemistry·N MasuyamaY Gotoh
Mar 9, 2002·Biochemical and Biophysical Research Communications·Neema Ganju, Alan Eastman
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jian YuLin Zhang
Aug 30, 2003·The Journal of Biological Chemistry·Xiaomin Mu, Chawnshang Chang
Nov 1, 2003·The International Journal of Biochemistry & Cell Biology·Xiao feng YeWen jin Su
Nov 13, 2003·Molecular and Cellular Biology·Siva Kumar KolluriXiao-kun Zhang
Oct 15, 2005·The Biochemical Journal·Andrew D WingateJ Simon C Arthur
Dec 8, 2006·Expert Opinion on Therapeutic Targets·Xiao-kun Zhang
Feb 14, 2007·Cancer Biology & Therapy·Hong YuXiaowei Xu
Jul 24, 2007·Archives of Biochemistry and Biophysics·Lynette J SchedlichRobert C Baxter
Mar 13, 2009·American Journal of Physiology. Cell Physiology·Paulette M Yamada, Kuk-Wha Lee
Aug 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aibo WangBarbara A Osborne

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Citations

Feb 7, 2019·Cellular and Molecular Life Sciences : CMLS·Hasanthi C de SilvaRobert C Baxter
Oct 6, 2017·BMC Complementary and Alternative Medicine·Qin JiangQi Zhang
Feb 15, 2020·Alcoholism, Clinical and Experimental Research·Mariana SaboyaWendie S Cohick
May 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yu QianXin Zhao
Feb 23, 2019·Journal of the Endocrine Society·Allyson Agostini-DreyerWendie S Cohick
Dec 13, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Yeon-Seop JungSyng-Ook Lee
Jul 5, 2016·Alcoholism, Clinical and Experimental Research·Catina Crismale-GannWendie S Cohick
Jun 2, 2020·Frontiers in Cell and Developmental Biology·Shailly Varma ShrivastavAnuraag Shrivastav
Oct 3, 2018·Molecular Medicine Reports·Lingjuan Wu, Liqun Chen
Mar 30, 2018·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J WuX Sun

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis