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A Rapid Degradation of Calponin 2 Is Required for Cytokinesis
American Journal of Physiology-Cell Physiology ( IF 5.0 ) Pub Date : 2021-06-16 , DOI: 10.1152/ajpcell.00569.2020
Airong Qian 1 , Tzu-Bou Hsieh 2 , M Moazzem Hossain 1 , Jim J-C Lin 3 , J-P Jin 1
Affiliation  

Calponin 2 is an actin cytoskeleton-associated protein and plays a role in regulating cell motility-related functions such as phagocytosis, migration and division. We previously reported that the expression of calponin 2 inhibits the rate of cell proliferation. To investigate the underlying mechanism, our present study found that the levels of endogenous calponin 2 in NIH3T3 and HEK293 cells rapidly decreased prior to cell division characterized by an absence at the actin contractile ring. In cells lacking endogenous calponin 2, transfective expression of GFP-fusion calponin 2 inhibited cell proliferation similar to that of non-fusion calponin 2. Fluorescent imaging studies of mitotic cells indicated that a proper level of calponin 2 expression and effective degradation during cytokinesis are necessary for normal cell division. Computer-assisted dynamic image analysis of dividing cells revealed that over-expression of calponin 2 significantly affects motile and shape behaviors of cells only on the interval from the start of anaphase to the start of cytokinesis, i.e., the pre-cytokinesis phase, but not on the interval from the start of cytokinesis to 50% completion of cytokinesis. The pre-cytokinesis degradation of calponin 2 was attenuated by MG132 inhibition of the ubiquitin proteasome and inhibitor of protein kinase C (PKC), suggesting that PKC phosphorylation-triggered degradation of calponin 2 could determine the rate of cytokinesis. The novel role of calponin 2 in regulating the rate of cytokinesis may be targeted for therapeutic applications such as in an inhibition of malignant tumor growth.

中文翻译:

细胞分裂需要钙调蛋白 2 的快速降解

Calponin 2 是一种肌动蛋白细胞骨架相关蛋白,在调节细胞运动相关功能(如吞噬、迁移和分裂)中发挥作用。我们之前报道过钙调蛋白 2 的表达抑制细胞增殖率。为了研究潜在机制,我们目前的研究发现,NIH3T3 和 HEK293 细胞中内源性钙调蛋白 2 的水平在细胞分裂前迅速下降,其特征是肌动蛋白收缩环缺失。在缺乏内源性钙调蛋白 2 的细胞中,GFP-融合钙调蛋白 2 的转染表达抑制细胞增殖,类似于非融合钙调蛋白 2。有丝分裂细胞的荧光成像研究表明,在胞质分裂过程中,钙调蛋白 2 的适当表达水平和有效降解是必要的用于正常的细胞分裂。计算机辅助的分裂细胞动态图像分析表明,calponin 2 的过表达仅在细胞分裂后期开始到细胞分裂开始的间隔,即细胞分裂前阶段,显着影响细胞的运动和形状行为,而不是从胞质分裂开始到胞质分裂完成 50% 的间隔。MG132 抑制泛素蛋白酶体和蛋白激酶 C (PKC) 抑制剂减弱了 calponin 2 的细胞分裂前降解,这表明 PKC 磷酸化触发的 calponin 2 降解可以决定细胞分裂的速率。钙调蛋白 2 在调节胞质分裂速率方面的新作用可能是治疗应用的目标,例如抑制恶性肿瘤的生长。
更新日期:2021-06-17
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