Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori.
Modification of eukaryotic proteins is a powerful strategy used by pathogenic bacteria to modulate host cells during infection. Previously, we demonstrated that Helicobacter pylori modify an unidentified protein within mammalian cell lysates in a manner consistent with the action of a bacterial ADP-ribosylating toxin. Here, we identified the modified eukaryotic factor as the abundant nuclear factor poly(ADP-ribose) polymerase-1 (PARP-1), which is important in the pathologies of several disease states typically associated with chronic H. pylori infection. However, rather than being ADP-ribosylated by an H. pylori toxin, the intrinsic poly(ADP-ribosyl) polymerase activity of PARP-1 is activated by a heat- and protease-sensitive H. pylori factor, resulting in automodification of PARP-1 with polymers of poly(ADP-ribose) (PAR). Moreover, during infection of gastric epithelial cells, H. pylori induce intracellular PAR-production by a PARP-1-dependent mechanism. Activation of PARP-1 by a pathogenic bacterium represents a previously unrecognized strategy for modulating host cell signaling during infection.
Nossa
Carlos W
CW
Department of Microbiology and the Institute for Genomic Biology and Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
Jain
Prashant
P
Tamilselvam
Batcha
B
Gupta
Vijay R
VR
Chen
Lin-Feng
LF
Schreiber
Valérie
V
Desnoyers
Serge
S
Blanke
Steven R
SR
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology; D006367:HeLa Cells; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
D010761:Phosphorus Radioisotopes; D000246:Adenosine Diphosphate Ribose; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases