Berndtsson Maria, Konishi Yoshiyuki, Bonni Azad, Hägg Maria, Shoshan Maria, Linder Stig, Havelka Aleksandra Mandic
Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
FEBS Lett. 2005 Jun 6;579(14):3090-4. doi: 10.1016/j.febslet.2005.04.067.
Phosphorylation of BCL-2 family member BAD at different residues triggers different physiological effects, either inhibiting or promoting apoptosis. The recently identified phosphorylation site at Ser-128 enhances the apoptotic activity of BAD. We here show that BAD becomes phosphorylated at Ser-128 in the mitotic phase of the cell cycle in NIH3T3 cells. We also show that BAD-S128 is phosphorylated in taxol-treated mouse fibroblasts and MDA-MB-231 human breast cancer cells. However, expression of a phosphorylation-defective dominant negative BAD mutant did not block taxol-induced apoptosis. These data support the view that the phosphorylation of BAD Serine 128 exerts cell-specific effects on apoptosis. Whereas the BAD Serine 128 phosphorylation induces apoptosis in neuronal cells, it does not appear to promote apoptosis in proliferating non-neural cells during mitosis or upon exposure to the antineoplastic agent taxol.
BCL-2家族成员BAD在不同残基处的磷酸化会引发不同的生理效应，要么抑制凋亡，要么促进凋亡。最近发现的丝氨酸128位点的磷酸化增强了BAD的凋亡活性。我们在此表明，在NIH3T3细胞的细胞周期有丝分裂期，BAD在丝氨酸128处发生磷酸化。我们还表明，在紫杉醇处理的小鼠成纤维细胞和MDA-MB-231人乳腺癌细胞中，BAD-S128发生了磷酸化。然而，磷酸化缺陷型显性负性BAD突变体的表达并未阻断紫杉醇诱导的凋亡。这些数据支持这样一种观点，即BAD丝氨酸128的磷酸化对凋亡具有细胞特异性作用。虽然BAD丝氨酸128的磷酸化在神经元细胞中诱导凋亡，但在有丝分裂期间或接触抗肿瘤药物紫杉醇时，它似乎并不会促进增殖的非神经细胞凋亡。
