Nuclear localisation is crucial for the proapoptotic activity of the HtrA-like serine protease Nma111p

• Published in: Journal of cell science Vol. 122; no. 21; pp. 3931 - 3941
• Main Authors: Belanger, Kenneth D, Walter, David, Henderson, Tracey A, Yelton, Allison L, O'Brien, Travis G, Belanger, Karyn G, Geier, Susan J, Fahrenkrog, Birthe
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01.11.2009
• Subjects: Amino Acid Motifs; Apoptosis; Cell Nucleus - chemistry; Cell Nucleus - enzymology; Cell Nucleus - genetics; Nuclear Localization Signals; Protein Transport; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Serine Endopeptidases - chemistry; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.056887

Programmed cell death is induced by the activation of a subset of intracellular proteins in response to specific extra- and intracellular signals. In the yeast Saccharomyces cerevisiae, Nma111p functions as a nuclear serine protease that is necessary for apoptosis under cellular stress conditions, such as elevated temperature or treatment of cells with hydrogen peroxide to induce cell death. We have examined the role of nuclear protein import in the function of Nma111p in apoptosis. Nma111p contains two small clusters of basic residues towards its N-terminus, both of which are necessary for efficient translocation into the nucleus. Nma111p does not shuttle between the nucleus and cytoplasm during either normal growth conditions or under environmental stresses that induce apoptosis. The N-terminal half of Nma111p is sufficient to provide the apoptosis-inducing activity of the protein, and the nuclear-localisation signal (NLS) sequences and catalytic serine 235 are both necessary for this function. We provide compelling evidence that intranuclear Nma111p activity is necessary for apoptosis in yeast.