Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Goulet B,Baruch A,Moon NS,Poirier M,Sansregret LL,Erickson A,Bogyo M,Nepveu Adoi
10.1016/s1097-2765(04)00209-6subject
Has Abstractpub_date
2004-04-23 00:00:00pages
207-19issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(04)00209-6journal_volume
14pub_type
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