Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Release of signal peptide fragments into the cytosol requires cleavage in the transmembrane region by a protease activity that is specifically blocked by a novel cysteine protease inhibitor JOURNAL OF BIOLOGICAL CHEMISTRY Weihofen, A., Lemberg, M. K., Ploegh, H. L., Bogyo, M., Martoglio, B. 2000; 275 (40): 30951-30956


    Signal peptides of secretory and membrane proteins are generated by proteolytic processing of precursor proteins after insertion into the endoplasmic reticulum membrane. Liberated signal peptides can be further processed, and the resulting N-terminal fragments are released toward the cytosol, where they may interact with target proteins like calmodulin. We show here that the processing of signal peptides requires a protease activity distinct from signal peptidase. This activity is inhibited specifically with a newly developed cysteine protease inhibitor, 1, 3-di-(N-carboxybenzoyl-l-leucyl-l-leucyl)amino acetone ((Z-LL)(2) ketone). Inhibitor studies revealed that the final, (Z-LL)(2) ketone-sensitive cleavage event occurs within the hydrophobic transmembrane region of the signal peptide, thus promoting the release of an N-terminal fragment into the cytosol.

    View details for Web of Science ID 000089762700032

    View details for PubMedID 10921927

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