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Guanosine 5′-diphosphate 3′ -diphosphate (ppGpp): Positive Effector for Histidine Operon Transcription and General Signal for Amino-Acid Deficiency
John C. Stephens, Stanley W. Artz and Bruce N. Ames
Proceedings of the National Academy of Sciences of the United States of America
Vol. 72, No. 11 (Nov., 1975), pp. 4389-4393
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/64962
Page Count: 5
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Maximal expression of the histidine operon of Salmonella typhimurium in a coupled in vitro transcription-translation system is strongly dependent upon addition of guanosine 5′-diphosphate 3′ -diphosphate (ppGpp). This requirement for ppGpp is exerted at the level of transcription through a mechanism distinct from the his-operon-specific regulatory mechanism. In vivo derepression of the his operon is markedly defective when histidine starvation is imposed on a relA mutant-unable to rapidly increase synthesis of ppGpp-growing in amino-acid-rich medium. Increased sensitivity of relA mutants to growth inhibition by a number of amino-acid analogs suggests that ppGpp is generally important in adjusting expression of amino-acid-producing systems. Analysis of these findings leads us to propose that ppGpp is a positive effector in a system that enables the cell to balance endogenous amino-acid production with environmental conditions of amino-acid availability, and to compensate efficiently for transient changes in these conditions. We propose a unifying theory of the role of ppGpp as the general signal molecule (alarmone) in a ``super-control'' which senses an amino-acid deficiency and redirects the cell's economy in response.
Proceedings of the National Academy of Sciences of the United States of America © 1975 National Academy of Sciences