A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells.
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.
Wang
G
G
Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, 1120 15th Street Room CB-2803, Augusta, GA 30912, USA.
Silva
J
J
Krishnamurthy
K
K
Bieberich
E
E
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation; D002458:Cell Fractionation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000199:Actins; D051017:Apoptosis Regulatory Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C101296:prostate apoptosis response-4 protein