Prostate apoptosis response gene-4 (par-4) abrogates the survival function of p185(BCR-ABL) in hematopoietic cells

Experimental Hematology
Natasa Kukoc-ZivojnovSimone Boehrer

Abstract

Prostate apoptosis response gene-4 (par-4) is deregulated in acute and chronic lymphatic leukemia. Given its pro-apoptotic role in neoplastic lymphocytes and evidence that par-4 antagonizes oncogenic Ras in solid tumors, we hypothesized that par-4 may act as a tumor suppressor impairing transformation induced by p185(BCR-ABL). The capacity of par-4 to interfere with factor independence induced by p185(BCR-ABL) and V12ras was evaluated by analysis of factor-independent growth of p185(BCR-ABL)/ par-4 and V12ras/par-4 transduced cells. The expression of par-4 and p185(BCR-ABL) by the respective constructs was controlled by Western blot analysis. Activated Ras was detected by pull-down assay in the cell clones expressing p185(BCR-ABL) in the absence and presence of par-4. Expression of p185(BCR-ABL) causes factor independence, signifying a conversion toward a transformed phenotype in hematopoietic precursors. We demonstrate that par-4 completely abolishes factor independence induced by p185(BCR-ABL) and partially abrogates factor independence caused by activated V12ras. Evaluating the underlying molecular mechanisms, we show that par-4 hinders activation of oncogenic Ras and causes concomitant disruptions of p185(BCR-ABL)-mediated ...Continue Reading

References

Oct 8, 1992·Nature·R P BissonnetteD R Green
Feb 1, 1991·Molecular and Cellular Biology·L VarticovskiL C Cantley
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·G Q Daley, D Baltimore
Sep 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J McLaughlinO N Witte
Sep 22, 1995·The Journal of Biological Chemistry·A J McGahonD R Green
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·I Sánchez-García, G Grütz
Oct 9, 1999·The Journal of Biological Chemistry·A NalcaV M Rangnekar
Oct 29, 1999·Genes & Development·C M EischenJ L Cleveland
Jun 13, 2000·Oncogene·P J CofferR P de Groot

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Citations

May 5, 2010·Oncogene·T Shrestha-Bhattarai, V M Rangnekar
Dec 31, 2005·Annals of the New York Academy of Sciences·Padhma Ranganathan, Vivek M Rangnekar
Feb 18, 2011·International Journal of Cancer. Journal International Du Cancer·Dongxiao ZhuangQingquan Li
Nov 27, 2018·Current Drug Targets·Renata Virgínia Cavalcanti SantosMichelly Cristiny Pereira

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