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Caspases disrupt the nuclear-cytoplasmic barrier.
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA.
The Journal of Cell Biology
|November 22, 2000
Summary
Caspase-9 inactivates nuclear transport during apoptosis, allowing caspase-3 to enter the nucleus and disassemble cellular components. This finding reveals a novel mechanism for nuclear targeting in programmed cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis involves caspases, proteases that dismantle cells by cleaving proteins.
- Caspase-3 is crucial for nuclear disassembly, but its cytoplasmic localization poses a targeting challenge.
- Previous hypotheses suggested active nuclear transport for caspase-3.
Purpose of the Study:
- To investigate the mechanism by which caspase-3 accesses nuclear targets during apoptosis.
- To elucidate the role of upstream caspases, specifically caspase-9, in regulating nuclear entry of caspase-3.
Main Methods:
- Investigated caspase activity and localization during apoptosis.
- Assessed the impact of caspase-9 on nuclear pore function and transport.
- Analyzed changes in nuclear pore diffusion limits.
Main Results:
- Caspase-9 activation precedes and affects nuclear transport.
- Caspase-9 inactivates active nuclear transport mechanisms.
- Nuclear pores exhibit increased diffusion limits post-caspase-9 activation, permitting passive entry of caspase-3.
Conclusions:
- Caspase-9 disrupts the nuclear-cytoplasmic barrier by altering nuclear pore permeability.
- This disruption facilitates caspase-3 diffusion into the nucleus, enabling nuclear apoptosis.
- Caspase-9 plays a key role in cell disassembly by controlling nuclear access during programmed cell death.