Functional implications of caspase-mediated RhoGDI2 processing during apoptosis of HL60 and K562 leukemia cells
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- 作者：Mi-Ran Choi ; Marcel Groot and Hannes C. A. Drexler
- 关键词：Apoptosis ; Proteasome inhibitor ; Staurosporine ; Rho GTPase ; RhoGDI2 ; Cleavage ; Localization ; Nuclear export
- 刊名：Apoptosis
- 出版年：2007
- 出版时间：November, 2007
- 年：2007
- 卷：12
- 期：11
- 页码：2025-2035
- 全文大小：759 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Cancer Research
Cell Biology
Biochemistry
Virology - 出版者：Springer Netherlands
- ISSN：1573-675X
文摘
RhoGDI2, a cytosolic regulator of Rho GTPase, is cleaved during apoptosis in a caspase-3 dependent fashion. By using 2D-gel electrophoresis, mass spectrometry and Western blotting we investigate in this paper the functional consequences of RhoGDI2 processing. We can show that loss of the N-terminal 19 amino acids results in a shift of the isoelectric point of the truncated RhoGDI2 (NΔ19) to a more basic value due to the removal of 9 acidic amino acids from the N-terminus, which may be responsible for enhanced retention of the N-terminally truncated protein within the nuclear compartment. Fusion of the p53 nuclear export signaling sequence MFRELNEALELK to NΔ19 (NΔ19NES) abolished its apoptosis promoting properties, while overexpression of NΔ19 significantly increased the susceptibility to apoptosis induction by the proteasome inhibitor PSI and by staurosporine. These results suggest that cleavage of RhoGDI2 by caspase-3 is not a functionally irrelevant bystander effect of caspase activation during apoptosis, but rather expedites progression of the apoptotic process.