Ondrousková Eva, Slovácková Jana, Pelková Vendula, Procházková Jirina, Soucek Karel, Benes Petr, Smarda Jan
Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlárská 2, CZ-611 37 Brno, Czech Republic.
Biol Chem. 2009 Jan;390(1):49-58. doi: 10.1515/BC.2009.007.
The Bcl-2 protein is one of the key components of biochemical pathways controlling programmed cell death. The function of this protein can be regulated by posttranslational modifications. Phosphorylation of Bcl-2 has been considered to be significantly associated with cell cycle arrest in the G2/M phase of the cell cycle, and with cell death caused by defects of microtubule dynamics. This study shows that phosphorylation of Bcl-2 can be induced by heavy metals due to activation of the Jun N-terminal kinase pathway that is not linked to the G2/M cell cycle arrest. Furthermore, we demonstrate that hyperphosphorylated Bcl-2 protein is a more potent inhibitor of zinc-induced cell death than its hypophosphorylated mutant form. These data suggest that regulation of Bcl-2 protein function by phosphorylation is an important part of cell responses to stress.
Bcl-2蛋白是控制程序性细胞死亡的生化途径的关键组成部分之一。该蛋白的功能可通过翻译后修饰来调节。Bcl-2的磷酸化被认为与细胞周期G2/M期的细胞周期停滞以及由微管动力学缺陷引起的细胞死亡显著相关。本研究表明，由于Jun N末端激酶途径的激活，重金属可诱导Bcl-2的磷酸化，而该途径与G2/M细胞周期停滞无关。此外，我们证明，与低磷酸化突变形式相比，高磷酸化的Bcl-2蛋白是锌诱导细胞死亡的更有效抑制剂。这些数据表明，通过磷酸化调节Bcl-2蛋白功能是细胞对应激反应的重要组成部分。
