Expression and function of the leucine zipper protein Par-4 in apoptosis

Author:

Sells S F1,Han S S1,Muthukkumar S1,Maddiwar N1,Johnstone R1,Boghaert E1,Gillis D1,Liu G1,Nair P1,Monnig S1,Collini P1,Mattson M P1,Sukhatme V P1,Zimmer S G1,Wood D P1,McRoberts J W1,Shi Y1,Rangnekar V M1

Affiliation:

1. Department of Surgery, University of Kentucky, Lexington 40536, USA.

Abstract

The prostate apoptosis response-4 (par-4) gene was identified by differential screening for genes that are upregulated when prostate cancer cells are induced to undergo apoptosis. The par-4 gene is induced by apoptotic signals but not by growth-arresting, necrotic, or growth-stimulatory signals. The deduced amino acid sequence of par-4 predicts a protein with a leucine zipper domain at its carboxy terminus. We have recently shown that the Par-4 protein binds, via its leucine zipper domain, to the zinc finger domain of Wilms' tumor protein WT1 (R. W. Johnstone et al., Mol. Cell. Biol. 16:6945-6956, 1996). In experiments aimed at determining the functional role of par-4 in apoptosis, an antisense par-4 oligomer abrogated par-4 expression and activator-driven apoptosis in rat prostate cancer cell line AT-3, suggesting that par-4 is required for apoptosis in these cells. Consistent with a functional role for par-4 in apoptosis, ectopic overexpression of par-4 in prostate cancer cell line PC-3 and melanoma cell line A375-C6 conferred supersensitivity to apoptotic stimuli. Transfection studies with deletion mutants of Par-4 revealed that full-length Par-4, but not mutants that lacked the leucine zipper domain of Par-4, conferred enhanced sensitivity to apoptotic stimuli. Most importantly, ectopic coexpression of the leucine zipper domain of Par-4 inhibited the ability of Par-4 to enhance apoptosis. Finally, ectopic expression of WT1 attenuated apoptosis, and coexpression of Par-4 but not a leucine zipperless mutant of Par-4 rescued the cells from the antiapoptotic effect of WT1. These findings suggest that the leucine zipper domain is required for the Par-4 protein to function in apoptosis.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Reference94 articles.

1. EGR-1 induction is required for maximal radiosensitivity in A375-C6 melanoma cells;Ahmed M.;J. Biol. Chem.,1996

2. The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo;Armstrong J. F.;Mech. Dev.,1993

3. Baglioni C. 1992. Mechanisms of cytotoxicity cytolysis and growth stimulation by TNF p. 425-438. In B. Beutler (ed.) Tumor necrosis factors: the molecules and their emerging role in medicine. Raven Press New York N.Y.

4. Boghaert E. R. S. F. Sells W. T. Al-Jumaily M. Weinstein N. Williams S. Strange and V. M. Rangnekar. Immunohistochemical analysis of Par-4 protein in diverse rat tissues. Submitted for publication.

5. Isolation and characterization of transcripts induced by androgen withdrawal and apoptotic cell death in the rat ventral prostate;Briehl M. M.;Mol. Endocrinol.,1991

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