Goulet Brigitte, Baruch Amos, Moon Nam-Sung, Poirier Madeleine, Sansregret Laurent L, Erickson Ann, Bogyo Matthew, Nepveu Alain
Department of Biochemistry, McGill University, 687 Pine Avenue West, Montreal H3A 1A1, Canada.
Mol Cell. 2004 Apr 23;14(2):207-19. doi: 10.1016/s1097-2765(04)00209-6.
The subclass of cysteine proteases termed lysosomal cathepsins has long been thought to be primarily involved in end-stage protein breakdown within lysosomal compartments. Furthermore, few specific protein substrates for these proteases have been identified. We show here that cathepsin L functions in the regulation of cell cycle progression through proteolytic processing of the CDP/Cux transcription factor. CDP/Cux processing in situ was increased following ectopic expression of cathepsin L but was reduced in Cat L(-/-) cells. Furthermore, catalytically active cathepsin L was localized to the nucleus during the G1-S transition as detected by immunofluorescence imaging and labeling using activity-based probes. Trafficking of cathepsin L to the nucleus is accomplished through a mechanism involving translation initiation at downstream AUG sites and the synthesis of proteases that are devoid of a signal peptide. Overall, these results uncover an as yet unsuspected role for cysteine proteases in the control of cell cycle progression.
长期以来，人们一直认为被称为溶酶体组织蛋白酶的半胱氨酸蛋白酶亚类主要参与溶酶体区室内的终末期蛋白质分解。此外，这些蛋白酶的特异性蛋白质底物很少被鉴定出来。我们在此表明，组织蛋白酶L通过对CDP/Cux转录因子进行蛋白水解加工，在细胞周期进程的调控中发挥作用。组织蛋白酶L异位表达后，原位的CDP/Cux加工增加，但在Cat L(-/-)细胞中减少。此外，通过免疫荧光成像和基于活性探针的标记检测到，在G1-S转换期间，具有催化活性的组织蛋白酶L定位于细胞核。组织蛋白酶L向细胞核的转运是通过一种机制完成的，该机制涉及下游AUG位点的翻译起始以及缺乏信号肽的蛋白酶的合成。总体而言，这些结果揭示了半胱氨酸蛋白酶在细胞周期进程控制中一个尚未被怀疑的作用。
