Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, UK.
Autophagy. 2011 Nov;7(11):1295-301. doi: 10.4161/auto.7.11.16646. Epub 2011 Nov 1.
(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery.
(宏观)自噬是一种膜运输过程,用于将细胞成分隔离在称为自噬体的细胞器中,自噬体将其靶向溶酶体进行降解。自噬在所有细胞中都以基础水平运作,作为维持细胞完整性的一种体内平衡机制。然而,自噬的水平和货物可以响应各种刺激而变化,并且自噬的扰动已知参与各种人类疾病的发病机制。因此,自噬必须受到严格控制。我们在这里报告,果蝇细胞周期蛋白依赖性激酶 PITSLRE 是自噬的调节剂。人 PITSLRE 同源物 CDK11 的缺失最初似乎诱导自噬,但在稍后的时间点,CDK11 对于自噬流和货物消化至关重要。由于 PITSLRE/CDK11 在果蝇和人类细胞中都调节自噬,因此该激酶代表自噬机制中的一个新的进化保守组成部分。