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J. Cell Biol. 151 (5): 951-960

Copyright © 2000 by the Rockefeller University Press.

Original Article

Caspases Disrupt the Nuclear-Cytoplasmic Barrier

Lavina Faleiroa,b, and Yuri Lazebnika

a Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724
b Molecular and Cell Biology Graduate Program, State University of New York at Stony Brook, Stony Brook, New York 11733
Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724.(516) 367 8461(516) 367 8363

Abstract: During apoptosis, caspases, a family of proteases, disassemble a cell by cleaving a set of proteins. Caspase-3 plays a major role in the disassembly of the nucleus by processing several nuclear substrates. The question is how caspase-3, which is usually cytoplasmic, gains access to its nuclear targets. It was suggested that caspase-3 is actively transported to the nucleus through the nuclear pores. We found that caspase-9, which is activated earlier than caspase-3, directly or indirectly inactivates nuclear transport and increases the diffusion limit of the nuclear pores. This increase allows caspase-3 and other molecules that could not pass through the nuclear pores in living cells to enter or leave the nucleus during apoptosis by diffusion. Hence, caspase-9 contributes to cell disassembly by disrupting the nuclear-cytoplasmic barrier.

Key Words: apoptosis • caspases • nuclear transport • nuclear pores

Abbreviations used in this paper: C9DN, caspase-9 dominant-negative mutant; DAPI, 4'6-diamidino-2-phenylindole; GFP, green fluorescent protein; NLS, nuclear localization signal.

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