PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression
PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression
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PDZRN3 通过维持细胞周期蛋白 A2 表达来防止成肌细胞凋亡
DOI：
10.1038/s41598-020-58116-1
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发表时间：
2020
影响因子：
4.6
通讯作者：
Inui M
中科院分区：
文献类型：
--
作者：
Honda T;Inui M
PDZRN 3是一种含有PDZ结构域的环指家族蛋白，在各种发育过程中发挥作用。我们先前的研究表明，在体内骨骼肌再生的早期阶段，PDZRN 3的表达与MyoD的表达一起被诱导。我们发现PDZRN 3以依赖于细胞周期蛋白A2的方式抑制成肌细胞凋亡并促进其增殖。通过RNA干扰消除小鼠C2 C12成肌细胞中的PDZRN 3降低Ki-67阳性细胞的比例和Akt磷酸化水平，暗示PDZRN 3在细胞增殖和凋亡的调节中起作用。将C2 C1/2细胞以及C3 H10 T1/2间充质干细胞和NIH-3 T3成纤维细胞暴露于包括血清剥夺在内的各种凋亡诱导剂，导致PDZRN 3耗尽细胞中裂解的半胱天冬酶-3的量比对照细胞中增加更大。在PDZRN 3缺失的C2 C12成肌细胞中，细胞周期蛋白A2的丰度降低，Mre 11的丰度也降低，这有助于DNA损伤的修复。细胞周期蛋白A2的过表达恢复了Mre 11和Ki-67的表达，并减弱了PDZRN 3缺失的细胞中的caspase-3裂解。这些结果表明，PDZRN 3通过维持细胞周期蛋白A2的表达，抑制成肌细胞和其他细胞类型的凋亡并促进增殖。
PDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regenerationin vivo. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression.