Zhang H, Heim J, Meyhack B
Oncology, Molecular Genetics, Novartis Pharma AG, Basel, CH- 4002, Switzerland.
Biochem Biophys Res Commun. 1998 Oct 20;251(2):454-9. doi: 10.1006/bbrc.1998.9485.
It is known that overexpression of Bax accelerates apoptosis, but the biochemical mechanism of the signal transduction from Bax to downstream targets has still not been fully determined. In the present study, we demonstrate that upon apoptotic stimuli, Bax moves from the cytosolic to the membrane fraction. The redistribution of Bax is not inhibited by a caspase inhibitor, zVAD-fmk, which blocks caspase-3 activity and prevents apoptosis in vivo. A FL5.12 Bax CL16 mutant cell, ms3, which is resistant to apoptosis induced by staurosporine, retains the activity of Bax redistribution but shows no caspase-3 activity. Our results revealed that Bax accumulation on membranes precedes caspase-3 activation, indicating that redistribution of Bax is an early event in apoptosis. These results suggest that Bax may be functionally significant in the regulation of caspase-3 activation.
已知Bax的过表达会加速细胞凋亡，但从Bax到下游靶点的信号转导的生化机制仍未完全确定。在本研究中，我们证明在凋亡刺激下，Bax从胞质转移到膜部分。Bax的重新分布不受半胱天冬酶抑制剂zVAD-fmk的抑制，zVAD-fmk可阻断半胱天冬酶-3的活性并在体内阻止细胞凋亡。对星形孢菌素诱导的细胞凋亡具有抗性的FL5.12 Bax CL16突变细胞ms3保留了Bax重新分布的活性，但没有半胱天冬酶-3的活性。我们的结果表明，Bax在膜上的积累先于半胱天冬酶-3的激活，这表明Bax的重新分布是细胞凋亡中的早期事件。这些结果表明，Bax在半胱天冬酶-3激活的调节中可能具有重要的功能意义。
