A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor

Brigitte Goulet; Amos Baruch; Nam-Sung Moon; Madeleine Poirier; Laurent L Sansregret; Ann Erickson; Matthew Bogyo; Alain Nepveu

doi:10.1016/s1097-2765(04)00209-6

A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor

Mol Cell. 2004 Apr 23;14(2):207-19. doi: 10.1016/s1097-2765(04)00209-6.

Authors

Brigitte Goulet¹, Amos Baruch, Nam-Sung Moon, Madeleine Poirier, Laurent L Sansregret, Ann Erickson, Matthew Bogyo, Alain Nepveu

Affiliation

¹ Department of Biochemistry, McGill University, 687 Pine Avenue West, Montreal H3A 1A1, Canada.

PMID: 15099520
DOI: 10.1016/s1097-2765(04)00209-6

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catalysis
Cathepsin L
Cathepsins / chemistry
Cathepsins / genetics
Cathepsins / metabolism*
Cell Cycle
Cell Extracts
Cell Nucleus / chemistry
Cell Nucleus / metabolism*
Chloroquine / pharmacology
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors / pharmacology
Dipeptides / pharmacology
Enzyme Activation
Fluorescent Antibody Technique, Indirect
Homeodomain Proteins
Leupeptins / pharmacology
Mice
NIH 3T3 Cells
Nuclear Proteins / drug effects
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Processing, Post-Translational / drug effects
Protein Sorting Signals*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Recombinant Proteins / metabolism
Repressor Proteins / drug effects
Repressor Proteins / genetics
Repressor Proteins / metabolism*
S Phase*
Subcellular Fractions

Substances

Cell Extracts
Cux1 protein, mouse
Cysteine Proteinase Inhibitors
Dipeptides
Homeodomain Proteins
Leupeptins
Nuclear Proteins
Protein Isoforms
Protein Sorting Signals
RNA, Messenger
Recombinant Proteins
Repressor Proteins
phenylalanyl-glycyl-NHO-Bz
Chloroquine
Cathepsins
Cysteine Endopeptidases
Cathepsin L
Ctsl protein, mouse
benzyloxycarbonylleucyl-leucyl-leucine aldehyde