Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis.

Nature
H SakahiraS Nagata

Abstract

Various molecules such as cytokines and anticancer drugs, as well as factor deprivation, rapidly induce apoptosis (programmed cell death), which is morphologically characterized by cell shrinkage and the blebbing of plasma membranes and by nuclear condensation. Caspases, particularly caspase 3, are proteases that are activated during apoptosis and which cleave substrates such as poly(ADP-ribose) polymerase, actin, fodrin, and lamin. Apoptosis is also accompanied by the internucleosomal degradation of chromosomal DNA. In the accompanying Article, we have identified and molecularly cloned a caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD). Here we show that caspase 3 cleaves ICAD and inactivates its CAD-inhibitory effect. We identified two caspase-3 cleavage sites in ICAD by site-directed mutagenesis. When human Jurkat cells were transformed with ICAD-expressing plasmid, occupation of the receptor Fas, which normally triggers apoptosis, did not result in DNA degradation. The ICAD transformants were also resistant to staurosporine-induced DNA degradation, although staurosporine still killed the cells by activating caspase. Our results indicate that activation of CAD downstream of the caspase cascade is responsibl...Continue Reading

References

Jan 1, 1992·Annual Review of Immunology·J J CohenK S Sellins
Sep 11, 1990·Nucleic Acids Research·S Mizushima, S Nagata
Jan 1, 1991·Annual Review of Cell Biology·R E EllisH R Horvitz
Jul 13, 1988·Biochimica Et Biophysica Acta·D LamarreG G Poirier
Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Jun 1, 1995·Current Opinion in Cell Biology·W C Earnshaw
Feb 7, 1997·Cell·S Nagata
Apr 11, 1997·The Journal of Biological Chemistry·R V TalanianW W Wong
Jul 1, 1997·The EMBO Journal·V L Longthorne, G T Williams
Feb 1, 1994·Trends in Cell Biology·M C PeitschJ Tschopp

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Citations

Jan 7, 2000·Journal of Cellular Physiology·S RokudaiT Tsuruo
Apr 22, 1999·Annals of Neurology·J B SchulzM A Moskowitz
Jul 19, 2002·The Anatomical Record·Wood Yee ChanDavid T Yew
Jan 25, 2002·International Journal of Cancer. Journal International Du Cancer·Ute A Sartorius, Peter H Krammer
Sep 28, 2002·International Journal of Cancer. Journal International Du Cancer·Michalis V KaramouzisHaralambos P Kalofonos
Jun 19, 2001·International Journal of Cancer. Journal International Du Cancer·E C ShinJ H Park
Aug 30, 2008·Science in China. Series C, Life Sciences·B QiQ Liu
Jul 9, 1998·Pathology Oncology Research : POR·R L RiceJ D Taylor
Mar 4, 2005·Archives of Pharmacal Research·Xian-Feng GongTakashi Ikejima
Apr 25, 2012·Archives of Toxicology·Supriya SwarnkarChandishwar Nath
Jul 26, 2005·Annals of Hematology·Katrien VermeulenZwi N Berneman
Oct 11, 2005·Apoptosis : an International Journal on Programmed Cell Death·S Singh, A Khar
May 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·H KanouchiS Toné
Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·M HamadaY Yura
Dec 30, 2006·Apoptosis : an International Journal on Programmed Cell Death·Min-Ju KimJae-Yong Lee
Jan 16, 2007·Apoptosis : an International Journal on Programmed Cell Death·Surajit KarmakarSwapan K Ray
Mar 21, 2006·Apoptosis : an International Journal on Programmed Cell Death·N HailM Andreeff
May 27, 2008·Apoptosis : an International Journal on Programmed Cell Death·Kazuhiko OmataTetsuro Suzuki
Apr 18, 2009·Apoptosis : an International Journal on Programmed Cell Death·Yael Feinstein-Rotkopf, Eli Arama
Nov 3, 2009·Apoptosis : an International Journal on Programmed Cell Death·Yiannis P NiniosThomae G Sourlingas
Aug 5, 2010·Apoptosis : an International Journal on Programmed Cell Death·Dror Mevorach
Dec 6, 2005·Biotechnology Letters·Bo-Eun KimIl-Seon Park
Sep 25, 2003·In Vitro Cellular & Developmental Biology. Animal·Kirsten H LimesandDavid O Quissell
Sep 13, 2013·Applied Biochemistry and Biotechnology·K RajaramP Sureshkumar
Jul 21, 2011·Pathology Oncology Research : POR·Zsuzsanna DunaiRudolf Mihalik
Nov 28, 2013·Cellular Oncology (Dordrecht)·Fatemeh BagheriNader Sheibani
Mar 17, 1999·Transplantation Proceedings·L GenestierJ P Revillard
Sep 28, 1998·Biochimica Et Biophysica Acta·S H Kaufmann

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