Nuclear Roles for Canonically Lysosomal Proteases.

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Cysteine proteases, traditionally lysosomal, are increasingly implicated in extralysosomal functions.
• Evidence suggests legumain and cathepsins play roles beyond the lysosome, including in the nucleus.

Purpose of the Study:

• To provide a comprehensive overview of nuclear translocation mechanisms for cysteine proteases.
• To summarize the known extralysosomal functions of these proteases within the nucleus.

Main Methods:

• Literature review of existing studies on protease translocation and nuclear function.
• Analysis of proposed mechanisms for nuclear import, including signal sequences and protein interactions.

Main Results:

• Discusses pathways for proteases to reach the cytosol (e.g., cytosolic translation, lysosomal permeabilization).
• Highlights nuclear functions such as cell cycle control, differentiation, apoptosis, immune response, and epigenetics.
• Identifies nuclear localization signals and protein 'hitchhiking' as potential transport mechanisms.

Conclusions:

• Cysteine proteases have significant extralysosomal roles, particularly in the nucleus.
• Further research using advanced profiling methods will uncover novel nuclear substrates and functions.
• Understanding nuclear protease activity is crucial for various cellular processes.