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J. Cell Biol. 159 (4): 637-648

Copyright © 2002 by the Rockefeller University Press.


A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis

Raymond Chiu1, Leonid Novikov1, Shaeri Mukherjee1, and Dennis Shields1,2

1 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461
2 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461

Address correspondence to Dennis Shields, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: (718) 430-2653. Fax: (718) 430-8567. E-mail: shields{at}

Abstract: In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining the structural organization of the Golgi apparatus. Here, we demonstrate that p115 was cleaved during apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those expressing a cleavage-resistant form of p115 delayed Golgi fragmentation during apoptosis. Expression of cDNAs encoding full-length or an NH2-terminal caspase cleavage fragment of p115 had no effect on Golgi morphology. In contrast, expression of the COOH-terminal caspase cleavage product of p115 itself caused Golgi fragmentation. Furthermore, this fragment translocated to the nucleus and its expression was sufficient to induce apoptosis. Most significantly, in vivo expression of the COOH-terminal fragment in the presence of caspase inhibitors, or upon coexpression with a cleavage-resistant mutant of p115, showed that p115 degradation plays a key role in amplifying the apoptotic response independently of Golgi fragmentation.

Key Words: Golgi apparatus; vesicular transport factor p115; apoptosis; caspases; Golgi matrix protein

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