Effects of Antibiotics and a Proto-Oncogene Homolog on Destruction of Protein Translocator SecY

• Published in: Science (American Association for the Advancement of Science) 2009-08, Vol.325 (5941), p.753-756
• Main Authors: van Stelten, Johna, Silva, Filo, Belin, Dominique, Silhavy, Thomas J
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Apoptosis; ATP-Dependent Proteases - metabolism; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; beta-Galactosidase - genetics; beta-Galactosidase - metabolism; Biological and medical sciences; Cell death; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Chloramphenicol - pharmacology; Cytoplasm; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Genes; Genetic mutation; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Hybridity; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Molecular and cellular biology; Mutant Proteins - metabolism; Periplasm; Periplasmic Proteins - genetics; Periplasmic Proteins - metabolism; Porins - genetics; Porins - metabolism; Protein secretion; Protein Sorting Signals; Protein Transport - drug effects; Proteins; Proto oncogenes; Receptors, Virus - genetics; Receptors, Virus - metabolism; Recombinant Fusion Proteins - metabolism; SEC Translocation Channels; Secretion; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Tetracycline - pharmacology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1172221

Protein secretion occurs via translocation by the evolutionarily conserved Sec complex. LacZ hybrid proteins have long been used to study translocation in Escherichia coli. Some LacZ hybrids were thought to block secretion by physically jamming the Sec complex, leading to cell death. We found that jammed Sec complexes caused the degradation of essential translocator components by the protease FtsH. Increasing the amounts or the stability of the membrane protein YccA, a known inhibitor of FtsH, counteracted this destruction. Antibiotics that inhibit translation elongation also jammed the translocator and caused the degradation of translocator components, which may contribute to their effectiveness. Intriguingly, YccA is a functional homolog of the proto-oncogene product Bax Inhibitor-1, which may share a similar mechanism of action in regulating apoptosis upon prolonged secretion stress.