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Cell. 2008 Jan 11;132(1):55-66. doi: 10.1016/j.cell.2007.11.044.

MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development.

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Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.


In prokaryotes, the toxin-antitoxin systems are thought to play important roles in growth regulation under stress conditions. In the E. coli MazE-MazF system, MazF toxin functions as an mRNA interferase cleaving mRNAs at ACA sequences to inhibit protein synthesis leading to cell growth arrest. Myxococcus xanthus is a bacterium displaying multicellular fruiting body development during which approximately 80% of cells undergo obligatory cell lysis. Here, we demonstrate that M. xanthus has a solitary mazF gene that lacks a cotranscribed antitoxin gene. The mazF deletion results in elimination of the obligatory cell death during development causing dramatic reduction in spore formation. Surprisingly, MrpC, a key developmental regulator, functions as a MazF antitoxin and a mazF transcription activator. Transcription of mrpC and mazF is negatively regulated via MrpC phosphorylation by a Ser/Thr kinase cascade. These findings reveal the regulated deployment of a toxin gene for developmental programmed cell death in bacteria.

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