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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:
 [1];  [2];  [1];  [1];  [1];  [3];  [4]
  1. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, University of Tokyo, Tokyo 113-8657 (Japan)
  2. (United States)
  3. Department of Pharmacology and Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 (United States)
  4. Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, University of Tokyo, Tokyo 113-8657 (Japan). E-mail: ashiota@mail.ecc.u-tokyo.ac.jp
Publication Date:
OSTI Identifier:
20798894
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 342; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.02.026; PII: S0006-291X(06)00314-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; GENE REGULATION; IN VITRO; LEUCINE; OLIGONUCLEOTIDES; PROMOTERS; PROTEINS; ULTRAVIOLET RADIATION

Citation Formats

Sun Weiyong, Department of Pharmacology and Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, Kimura, Hiromichi, Hattori, Naka, Tanaka, Satoshi, Matsuyama, Shigemi, and Shiota, Kunio. Proliferation related acidic leucine-rich protein PAL31 functions as a caspase-3 inhibitor. United States: N. p., 2006. Web.
Sun Weiyong, Department of Pharmacology and Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, Kimura, Hiromichi, Hattori, Naka, Tanaka, Satoshi, Matsuyama, Shigemi, & Shiota, Kunio. Proliferation related acidic leucine-rich protein PAL31 functions as a caspase-3 inhibitor. United States.
Sun Weiyong, Department of Pharmacology and Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, Kimura, Hiromichi, Hattori, Naka, Tanaka, Satoshi, Matsuyama, Shigemi, and Shiota, Kunio. Fri . "Proliferation related acidic leucine-rich protein PAL31 functions as a caspase-3 inhibitor". United States. doi:.
@article{osti_20798894,
title = {Proliferation related acidic leucine-rich protein PAL31 functions as a caspase-3 inhibitor},
author = {Sun Weiyong and Department of Pharmacology and Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 and Kimura, Hiromichi and Hattori, Naka and Tanaka, Satoshi and Matsuyama, Shigemi and Shiota, Kunio},
abstractNote = {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.},
doi = {},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 342,
place = {United States},
year = {Fri Apr 14 00:00:00 EDT 2006},
month = {Fri Apr 14 00:00:00 EDT 2006}
}
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