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Updated: Aug 11, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Cathepsins as transcriptional activators?
1Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, 513 Parnassus Avenue, HSE-201, San Francisco, CA 94143, USA.
Developmental Cell
|May 8, 2004
Summary
Researchers discovered a lysosomal protease, cathepsin L, in a new form that enters the nucleus. This nuclear cathepsin L activates the CDP/Cux transcription factor, revealing a novel signaling pathway.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Protease Function
Background:
- Proteases regulate cellular processes through limited cleavage of target proteins.
- Transcription factors are key regulators of gene expression, often activated by post-translational modifications.
- Nuclear signaling pathways control gene transcription and cellular responses.
Purpose of the Study:
- To investigate the nuclear roles of proteases beyond their canonical functions.
- To identify novel mechanisms regulating transcription factor activity.
- To explore the function of cathepsin L in nuclear signaling pathways.
Main Methods:
- Utilized biochemical assays to detect protease activity in nuclear fractions.
- Employed immunofluorescence and cell fractionation to determine cathepsin L localization.
- Performed reporter gene assays to assess the activation of the CDP/Cux transcription factor.
Main Results:
- Identified a previously unrecognized nuclear-trafficking isoform of cathepsin L.
- Demonstrated that nuclear cathepsin L directly cleaves and activates the CDP/Cux transcription factor.
- Showcased the role of this lysosomal protease in initiating nuclear signaling cascades.
Conclusions:
- Lysosomal proteases, such as cathepsin L, can exert functions within the nucleus.
- The nuclear activity of cathepsin L provides a novel mechanism for regulating transcription factor activity.
- These findings open new avenues for research into nuclear proteases and their roles in cell signaling.
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