Phosphorylation site mutated RB exerts contrasting effects on apoptotic response to different stimuli.
Phosphorylation site mutated RB exerts contrasting effects on apoptotic response to different stimuli.
复制标题
磷酸化位点突变的 RB 对不同刺激的细胞凋亡反应产生不同的影响。
作者：
Masselli,A;Wang,JYJ
视网膜母细胞瘤肿瘤抑制蛋白(Rb)是细胞周期和细胞凋亡的重要调节因子。Rb在细胞周期进程中被细胞周期蛋白依赖的蛋白激酶磷酸化。磷酸化位点突变(Psm)-Rb此前已被证明可导致G1期停滞，并干扰S的细胞周期进展。在这项研究中，我们研究了可诱导的PSM-Rb表达对三种不同的死亡刺激：阿霉素(Doxo)、星形孢子素(STS)和肿瘤坏死因子(TNF)对大鼠16细胞凋亡反应的影响。PSM-Rb的诱导表达可减弱Doxo引起的细胞周期停滞所致的caspase活性。已有研究表明，STS可导致Rb依赖的G1期细胞停滞或凋亡；然而，PSM-Rb的表达并不能阻止STS对caspase的激活。令人惊讶的是，PSM-Rb的诱导表达刺激了大鼠-16细胞对肿瘤坏死因子的凋亡反应，在没有PSM-Rb的情况下，这些细胞大多会发生坏死。这些结果表明，PSM-Rb对不同刺激的凋亡反应具有不同的影响，细胞周期停滞并不总是与抗凋亡相关。
The retinoblastoma tumor-suppressor protein (RB) is an important regulator of cell cycle and apoptosis. RB is phosphorylated by cyclin-dependent protein kinase during cell cycle progression. A phosphorylation site mutated (PSM)-RB has previously been shown to cause G1 arrest and to interfere with S phase progression. In this study, we examined the effect of inducible PSM-RB expression on the apoptotic response to three different death stimuli: doxorubicin (DOXO), staurosporine (STS) and tumor necrosis factor (TNF) in Rat-16 cells. Induced expression of PSM-RB attenuated caspase activation by DOXO as a result of cell cycle arrest. STS has been shown to cause RB-dependent G1 arrest or apoptosis; however, expression of PSM-RB did not prevent caspase activation by STS. Surprisingly, induced expression of PSM-RB stimulated the apoptotic response to TNF in Rat-16 cells, which mostly undergo necrosis in the absence of PSM-RB. These results show that PSM-RB exerts disparate effects on apoptotic response to different stimuli, and that cell cycle arrest does not always associate with resistance to apoptosis.