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J. Cell Biol. 149 (3): 603-612

Copyright © 2000 by the Rockefeller University Press.

© The Rockefeller University Press, /2000/5/603/ $5.00
The Journal of Cell Biology, Volume 149, Number 3, May 1, 2000 603-612
Original Article Caspase-2 Is Localized at the Golgi Complex and Cleaves Golgin-160 during Apoptosis Marie Mancinia, Carolyn E. Machamerb, Sophie Roye, Donald W. Nicholsone, Nancy A. Thornberryf, Livia A. Casciola-Rosenb,c, and Antony Rosena,b,d a Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 b Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 c Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 d Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 e Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Pointe Claire-Dorval, Quebec, H9R 4P8, Canada f Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065 Antony Rosen, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Room 1059, Baltimore, MD 21205. Tel:(410) 955-0139 Fax:(410) 955-0964 E-mail:arosen{at}jhmi.edu.

Caspases are an extended family of cysteine proteases that play critical roles in apoptosis. Animals deficient in caspases-2 or -3, which share very similar tetrapeptide cleavage specificities, exhibit very different phenotypes, suggesting that the unique features of individual caspases may account for distinct regulation and specialized functions. Recent studies demonstrate that unique apoptotic stimuli are transduced by distinct proteolytic pathways, with multiple components of the proteolytic machinery clustering at distinct subcellular sites. We demonstrate here that, in addition to its nuclear distribution, caspase-2 is localized to the Golgi complex, where it cleaves golgin-160 at a unique site not susceptible to cleavage by other caspases with very similar tetrapeptide specificities. Early cleavage at this site precedes cleavage at distal sites by other caspases. Prevention of cleavage at the unique caspase-2 site delays disintegration of the Golgi complex after delivery of a pro-apoptotic signal. We propose that the Golgi complex, like mitochondria, senses and integrates unique local conditions, and transduces pro-apoptotic signals through local caspases, which regulate local effectors.

signaling, subcellular, substrate, coiled coil, protease

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