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A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells

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Abstract

The elevated expression of prostate apoptosis response-4 (PAR-4) induces apoptosis in differentiating mouse embryonic stem (ES) cells. In embryoid body (EB) cells and the E15.5 stage of embryonic mouse brain, PAR-4 is expressed as two isoforms (38 and 33 kDa). Using mouse EB-derived RNA as a template we have cloned and characterized a novel isoform of PAR-4 (PAR-4/p33) that lacks exon 3 and shows a bona fide splice junction of exons 2 and 4. The molecular mass for PAR-4/p33 is estimated to be 33 kDa, corresponding to the short form found in the EB cells and E15.5 mouse brain. The fluorescent fusion protein of PAR-4/p33 is mainly found in the cytosol and is co-distributed with F-actin filaments, while that of the 38 kDa full length PAR-4/p38 is predominantly translocated to the nucleus. In contrast to the full length PAR-4 (PAR-4/p38), ectopic expression of PAR-4/p33 does not result in the activation of caspase 3 and the induction of apoptosis. PAR-4/p33 forms a complex with PAR-4/p38, which inhibits its nuclear translocation and the induction of apoptosis. PAR-4/p33 is suggested to be a dominant negative isoform of PAR-4/p38 and may regulate PAR-4-dependent apoptosis.

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Authors and Affiliations

  1. Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, 1120 15th Street Room CB-2803, Augusta, 30912, GA, Italy

    G. Wang, J. Silva, K. Krishnamurthy & E. Bieberich

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  1. G. Wang
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  2. J. Silva
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  3. K. Krishnamurthy
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  4. E. Bieberich
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Correspondence to E. Bieberich.

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Wang, G., Silva, J., Krishnamurthy, K. et al. A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells. Apoptosis 11, 315–325 (2006). https://doi.org/10.1007/s10495-006-3979-8

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  • DOI: https://doi.org/10.1007/s10495-006-3979-8

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