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Sci. STKE, 4 May 2004
Vol. 2004, Issue 231, p. tw156
[DOI: 10.1126/stke.2312004TW156]


CELL CYCLE Cathepsin L, Not Just for Lysosomes Anymore

Transcription factors of the CDP/Cux family are homologs of the Drosophila Cut protein and are implicated in control of cell proliferation. In mammals, phosphorylation state and specific proteolytic cleavage control the transcriptional regulatory activity of CDP/Cux. The dephosphorylated, cleaved p110 form stably interacts with DNA and stimulates expression of genes involved in DNA replication, such as the gene encoding DNA polymerase α. Goulet et al. determined that proteolytic processing of CDP/Cut was mediated by cathepsin L (a cysteine peptidase best known for its function in lysosomes), which accumulated in the nucleus as cells progressed from G1 to S phase. Furthermore, nuclear accumulation of cathepsin L was associated with use of downstream start codons for initiation of translation of cathepsin transcripts such that a protein lacking the signal peptide was synthesized (the signal peptide directs cathepsin L to the lysosome during biosynthesis). Thus, there appears to be a mechanism for regulating translation start choice during cell cycle progression that allows altered cellular localization of the cathepsin L protease, which is responsible for cleavage and activation of the CDP/Cux transcription factors.

B. Goulet, A. Baruch, N.-S. Moon, M. Poirier, L. L. Sansregret, A. Erickson, M. Bogyo, A. Nepveu, A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cus transcription factor. Mol. Cell 14, 207-219 (2004). [Online Journal]

Citation: Cathepsin L, Not Just for Lysosomes Anymore. Sci. STKE 2004, tw156 (2004).

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