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Updated: Aug 8, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Essential role of active nuclear transport in apoptosis
N Yasuhara1, Y Eguchi, T Tachibana
1Department of Medical Genetics, Biomedical Research Centre, Osaka University Medical School, Suita, Japan.
Background:
Apoptosis is defined by chromatin condensation, nuclear fragmentation and the formation of apoptotic bodies. Because apoptotic signals are transmitted through a common pathway that includes the target steps of death-driving ICE-family proteases and anti-cell death protein Bcl-2 in the cytoplasm, the signals must be transferred from the cytoplasm to the nucleus, at least to induce the apoptotic manifestation of the nucleus. Small signal molecules might diffuse across nuclear pores, but larger molecules are transported by active mechanisms requiring ATP and GTP hydrolysis. It is not known whether apoptotic signals are transmitted into the nucleus by the mechanisms of active nuclear transport.
Results:
To test the possibility that active nuclear transport is involved in apoptotic signal transmission, we have analysed the effects of molecules that inhibit active nuclear transport on apoptosis. Wheat germ agglutinin (WGA), excess amounts of p10 protein, Ran-GTPgammaS complex, and anti-PTAC58 antibody, which all inhibit active nuclear transport when exogenously microinjected, prevent Fas-induced apoptotic nuclear manifestation. WGA also prevents apoptotic nuclear change promoted by microinjected active CPP32beta/Yama protease (an ICE family member), which plays an essential role in most apoptosis.
Conclusions:
The results presented here strongly suggest that active nuclear transport is essential for apoptotic signal transduction.
Insights
Active nuclear transport is essential for apoptosis signaling. Inhibiting this transport prevents nuclear changes associated with programmed cell death, indicating its critical role in the apoptotic pathway.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- Apoptosis involves nuclear changes like chromatin condensation and fragmentation.
- Apoptotic signals use cytoplasmic pathways involving ICE-family proteases and Bcl-2.
- Signal transmission from cytoplasm to nucleus is necessary for nuclear apoptotic manifestation.
Purpose of the Study:
- To investigate if active nuclear transport mechanisms are involved in transmitting apoptotic signals to the nucleus.
- To determine the role of active nuclear transport in the overall process of apoptosis.
Main Methods:
- Microinjection of inhibitors of active nuclear transport into cells.
- Analysis of the effects of these inhibitors on Fas-induced apoptosis.
- Assessment of inhibition on apoptosis induced by microinjected CPP32beta/Yama protease.
Main Results:
- Inhibitors of active nuclear transport, including Wheat germ agglutinin (WGA), prevent Fas-induced apoptotic nuclear changes.
- WGA also blocks apoptosis-related nuclear changes induced by active CPP32beta/Yama protease.
- These findings demonstrate that active nuclear transport is required for apoptotic signal transduction.
Conclusions:
- Active nuclear transport is a critical component of apoptotic signal transduction.
- Blocking active nuclear transport effectively inhibits the progression of apoptosis.
- The study provides strong evidence for the necessity of nuclear transport in programmed cell death.
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