LEUCINE-RESPONSIVE REGULATORY PROTEIN: A Global Regulator of Gene Expression in <i>E. Coli</i>

Newman, E. B.; Lin, Rongtuan

doi:10.1146/annurev.mi.49.100195.003531

Cited by 150 publications

(70 citation statements)

References 40 publications

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“…A transcriptional regulator of the Lrp͞AsnC family was up-regulated in early S phase. Homologs of this protein act as global metabolic regulators and are involved in the control of amino acid metabolism in a number of different bacteria, making this protein a candidate for cell cycle control of amino acid biosynthesis (42)(43)(44)(45). Several enzymes involved in riboflavin and tetrahydrofolate biosynthesis had a sharp expression peak in G 1 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Proteomic analysis of the bacterial cell cycle

Grünenfelder

Rummel

Vohradský

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

122

101

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A global approach was used to analyze protein synthesis and stability during the cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth (979) of the estimated C. crescentus gene products were detected by two-dimensional gel electrophoresis, 144 of which showed differential cell cycle expression patterns. Eighty-one of these proteins were identified by mass spectrometry and were assigned to a wide variety of functional groups. Pattern analysis revealed that coexpression groups were functionally clustered. A total of 48 proteins were rapidly degraded in the course of one cell cycle. More than half of these unstable proteins were also found to be synthesized in a cell cycle-dependent manner, establishing a strong correlation between rapid protein turnover and the periodicity of the bacterial cell cycle. This is, to our knowledge, the first evidence for a global role of proteolysis in bacterial cell cycle control.

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Section: Resultsmentioning

confidence: 99%

Proteomic analysis of the bacterial cell cycle

Grünenfelder

Rummel

Vohradský

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

122

101

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“…2 The results of these experiments showed that L-leucine coordinately destabilizes all of the Lrp-DNA complexes. The apparent macroscopic inhibition constant (K i ) for this L-leucine-mediated inhibition of Lrp-DNA binding activity, measured by the appearance of the uncomplexed (free) DNA fragment, is approximately 2 mM.…”

Section: Identification Of An Lrp Consensus-like Dna-binding Site In mentioning

confidence: 95%

Leucine-responsive Regulatory Protein-DNA Interactions in the Leader Region of the ilvGMEDA Operon of Escherichia coli

Rhee

Parekh

Hatfield

1996

Journal of Biological Chemistry

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The leucine-responsive regulatory protein, Lrp, 1 is a global regulatory protein of Escherichia coli that affects the expression of many operons (reviewed in Refs. 1 and 2). The expression of some target operons is activated by Lrp, while the expression of others is repressed. In addition, the free amino acid, L-leucine, acts as an effector ligand of Lrp; and, at some DNA target sites, L-leucine is required for Lrp binding. At other sites, L-leucine can antagonize or have no effect on Lrp-DNA interactions. In most cases, the physiological role of Lrp is to activate biosynthetic operons and to repress degradative ones. Therefore, it has been suggested that Lrp and L-leucine might function to coordinate metabolic shifts between nutritional feast and famine conditions. However, the metabolic coherence of the operons regulated by Lrp remains unclear.The structural gene for Lrp was initially identified as a mutation in a regulatory gene, livR, for the branched-chain amino acid (L-leucine, L-isoleucine, and L-valine) transport system (3). Subsequently, additional mutations in this gene that affected the biosynthesis of L-leucine were identified (4). Further studies showed that the protein product of this gene (now referred to as lrp) activates transcription of the ilvIH operon, which encodes one of the three acetohydroxy acid synthase (AHAS) isozymes required for the first step in the biosynthesis of the three branched-chain amino acids (4). Interestingly, many of the other operons regulated by Lrp are involved in either the production or the dissimilation of the carbon substrates, pyruvate and ␣-ketobutyrate, of the AHAS isozymes required for branched-chain amino acid biosynthesis (Fig. 1). For example, Lrp regulates the serA and sdaA genes involved in the production of pyruvate and the tdh and kbl genes, which affect the in vivo levels of L-threonine and ␣-ketobutyrate (5, 6). Also, Lrp regulates the expression of the leucine biosynthetic operon, leuABCD (7), and the expression of the branched-chain amino acid transport genes livJ and livKHMG (8). Thus, it appears that Lrp plays an important role in the maintenance of appropriate in vivo levels of the branched-chain amino acids. Such a role for Lrp in branched-chain amino acid metabolism is further underscored by the partial auxotrophy for the branched-chain amino acids observed in a lrp Ϫ strain of E. coli K12 (1).In E. coli, the biosynthesis of the branched-chain amino acids occurs via a parallel pathway catalyzed by several bifunctional enzymes ( Fig. 1) (9). The genes encoding these enzymes are specified by four separate operons (ilvBN, ilvGMEDA, ilvYC, and ilvIH). The ilvBN and ilvIH operons encode the genes for the subunits of the AHAS I and AHAS III isozymes, respectively (10). The ilvGMEDA operon encodes four of the five enzymes required for the biosynthesis of L-isoleucine and Lvaline (11). The ilvGM genes encode the subunits of AHAS I, while the remaining genes encode two other enzymes of the common pathway, dihydroxy-acid dehydratase (ilvD) and transamin...

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“…30) Lrp senses the presence of rich nutrition by interacting with leucine, and functions as a transcriptional repressor as well as an activator, thereby regulating 40-70 transcription units. [3][4][5] Generally, biosynthetic pathways functioning in autotrophic metabolism are activated by Lrp, whereas, catabolic pathways functioning in heterotrophic metabolism are repressed. In general, repression can be achieved by blocking the approach of RNA polymerase by binding of a repressor to the promoter, or by blocking extension of the mRNA by binding of a repressor further downstream.…”

Section: ) Similarities Between Regulations By Eubac-terial Lrp Andmentioning

confidence: 99%

“…Sensing the presence of rich nutrition by the concentration of leucine, E. coli shifts its metabolism from the "famine" to "feast" mode, thereby regulating 40-70 transcription units, [3][4][5] using ca. 3000 Lrp dimers present per cell.…”

Section: Introductionmentioning

confidence: 99%