INSERM, UMR892, CRCNA, Institut de Recherche thérapeutique de l'Université de Nantes, 44007 Nantes Cedex1, France.
FEBS Lett. 2010 Feb 5;584(3):487-92. doi: 10.1016/j.febslet.2009.11.094. Epub 2009 Dec 4.
Mcl-1 full-length (Mcl-1(1-350)), a tightly regulated protein, plays an important role in protecting cells against apoptosis. Cleavage of Mcl-1 at Asp127 by caspase (Mcl-1(C1)) contributes to the regulation of Mcl-1 expression, but its pro-apoptotic function remains controversial. Here, we reported that Mcl-1(128-350) expression induced caspase-dependent apoptosis. We demonstrated that Mcl-1(128-350) but not Mcl-1(1-350) interacts with Bax. This interaction required an intact BH3 Mcl-1(128-350) domain and leads to Bax activation and translocation to mitochondria. The silencing of Bax, but not of Bak, prevented Mcl-1(128-350) induced apoptosis. In conclusion, Mcl-1(128-350) exerts a pro-apoptotic function governed by its capacity to interact with Bax.
Mcl-1 全长（Mcl-1(1-350)）是一种受严格调控的蛋白质，在保护细胞免受凋亡方面发挥着重要作用。半胱天冬酶（caspase）在天冬氨酸 127 位切割 Mcl-1（Mcl-1(C1)）有助于调节 Mcl-1 的表达，但它的促凋亡功能仍存在争议。在这里，我们报道了 Mcl-1(128-350)的表达诱导了 caspase 依赖性凋亡。我们证明了 Mcl-1(128-350)而不是 Mcl-1(1-350)与 Bax 相互作用。这种相互作用需要完整的 BH3 Mcl-1(128-350)结构域，并导致 Bax 激活和向线粒体的易位。 Bax 的沉默，但不是 Bak 的沉默，阻止了 Mcl-1(128-350)诱导的凋亡。总之，Mcl-1(128-350)通过与 Bax 相互作用发挥促凋亡功能。
