Journal article

XIAP discriminates between type I and type II FAS-induced apoptosis

Philipp J Jost, Stephanie Grabow, Daniel Gray, Mark D McKenzie, Ueli Nachbur, David CS Huang, Philippe Bouillet, Helen E Thomas, Christoph Borner, John Silke, Andreas Strasser, Thomas Kaufmann

Nature | NATURE PUBLISHING GROUP | Published : 2009

Abstract

FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of..

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Grants

Awarded by NCI


Awarded by Leukemia and Lymphoma Society of America


Awarded by German Jose Carreras Leukemia Foundation


Awarded by Spemann Graduate School of Biology and Medicine



Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

We thank D. Vaux, J. Tschopp, S. Cory, J. Adams, S. Nagata and Y. Lazebnik for gifts of mice and reagents, K. Vella, D. Cooper and G. Siciliano for animal care, B. Helbert for genotyping, the Biochemistry Department of the Royal Melbourne Hospital for ALT/AST measurements, C. Young and D. Chau for technical assistance and D. Vaux, M. Van Delft and L. O'Reilly for advice. This work was supported by grants ( programmes 257502 and 251608; project 384404) and fellowships from the NHMRC ( Canberra), NCI ( NIH, CA 80188, CA 43540), Leukemia and Lymphoma Society of America ( SCOR grant 7015), JDRF/ NHMRC, Cancer Council Victoria, Leukemia Foundation of Australia, Swiss National Science Foundation ( T. K. and U. N.), Novartis Jubilaeumsstiftung ( U. N.), HepatoSys programme ( BMBF), German Jose Carreras Leukemia Foundation ( DJCLS R 06/09), Spemann Graduate School of Biology and Medicine ( GSC-4), DFG ( to C. B.) and Dr. Mildred-Scheel Stiftung/Deutsche Krebshilfe ( P. J. J.).