Null mutations in a Nudix gene, ygdP, implicate an alarmone response in a novel suppression of hybrid jamming.
Induction of the toxic LamB-LacZ protein fusion, Hyb42-1, leads to a lethal generalized protein export defect. The prlF1 suppressor causes hyperactivation of the cytoplasmic Lon protease and relieves the inducer sensitivity of Hyb42-1. Since prlF1 does not cause a detectable change in the stability or level of the hybrid protein, we conducted a suppressor screen, seeking factors genetically downstream of lon with prlF1-like phenotypes. Two independent insertions in the ygdP open reading frame relieve the toxicity of the fusion protein and share two additional properties with prlF1: cold sensitivity and the ability to suppress the temperature sensitivity of a degP null mutation. Despite these similarities, ygdP does not appear to act in the same genetic pathway as prlF1 and lon, suggesting a fundamental link between the phenotypes. We speculate that the common properties of the suppressors relate to secretion defects. The ygdP gene (also known as nudH) has been shown to encode a Nudix protein that acts as a dinucleotide oligophosphate (alarmone) hydrolase. Our results suggest that loss of ygdP function leads to the induction of an alarmone-mediated response that affects secretion. Using an epitope-tagged ygdP construct, we present evidence that this response is sensitive to secretion-related stress and is regulated by differential proteolysis of YgdP in a self-limiting manner.
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Nicholas J
NJ
Hand
Thomas J
TJ
Silhavy
D001425:Bacterial Outer Membrane Proteins; D003080:Cold Temperature; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response; D007763:Lac Operon / Q000235:genetics / Q000502:physiology; D008320:Maltose / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018272:Porins; D011755:Pyrophosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D013489:Suppression, Genetic; D000096964:Nudix Hydrolases
D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; D008320:Maltose; D018272:Porins; D011755:Pyrophosphatases; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D000096964:Nudix Hydrolases; C016532:maltoporins