Puromycin-sensitive aminopeptidase: Sequence analysis, expression, and functional characterization

Daniel B. Constam, Andreas R. Tobler, Anne Rensing-Ehl, Iris Kemler, Louis B. Hersh, Adriano Fontana

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Among the molecular mechanisms that control the cell division cycle, proteolysis has emerged as a key regulatory process enabling cells to pass critical check points. Such proteolysis involves a cascade of enzymes including a multisubunit complex termed 26S proteasome. Here we report on the analysis of a novel mouse cDNA encoding the puromycin-sensitive aminopeptidase (PSA) and on its expression in COS cells and 3T3 fibroblasts. PSA is 27-40% homologous to several known Zn2+-binding aminopeptidases including aminopeptidase N. Immunohistochemical analysis revealed that PSA is localized to the cytoplasm and to the nucleus and associates with microtubules of the spindle apparatus during mitosis. Furthermore, puromycin and bestatin both arrested the cell cycle, leading to an accumulation of cells in G2/M phase, and ultimately induced cells to undergo apoptosis at concentrations that inhibit PSA. Control experiments including cycloheximide further suggested that the induction of apoptosis by puromycin was not attributable to inhibition of protein synthesis. Taken together, these data favor the novel idea that PSA participates in proteolytic events essential for cell growth and viability.

Original languageEnglish
Pages (from-to)26931-26939
Number of pages9
JournalJournal of Biological Chemistry
Volume270
Issue number45
DOIs
StatePublished - Nov 10 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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