title: Proliferation related acidic leucine-rich protein PAL31 functions as a caspase-3 inhibitor.
abstract: Proliferation related acidic leucine-rich protein PAL31 (PAL31) is expressed in proliferating cells and consists of 272 amino acids with a tandem structure of leucine-rich repeats in the N-terminus and a highly acidic region with a putative nuclear localization signal in the C-terminus. We previously reported that PAL31 is required for cell cycle progression. In the present study, we found that the antisense oligonucleotide of PAL31 induced apoptosis to the transfected Nb2 cells. Stable transfectants, in which PAL31 was regulated by an inducible promoter, were generated to gain further insight into the signaling role of PAL31 in the regulation of apoptosis. Expression of PAL31 resulted in the marked rescue of Rat1 cells from etoposide and UV radiation-induced apoptosis and the cytoprotection was correlated with the levels of PAL31 protein. Thus, cytoprotection from apoptosis is a physiological function of PAL31. PAL31 can suppress caspase-3 activity but not cytochrome c release in vitro, indicating that PAL31 is a direct caspase-3 inhibitor. In conclusion, PAL31 is a multifunctional protein working as a cell cycle progression factor as well as a cell survival factor.
authors.affiliation: Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Sun
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kimura
authors.forename: Naka
authors.initials: N
authors.lastname: Hattori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shigemi
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D014466:Ultraviolet Rays
chemical_list: C412378:Anp32b protein, rat; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D005047:Etoposide; D010749:Phosphoprotein Phosphatases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases