PMID- 28406453
OWN - NLM
STAT- MEDLINE
DCOM- 20170803
LR  - 20211204
IS  - 2072-6651 (Electronic)
IS  - 2072-6651 (Linking)
VI  - 9
IP  - 4
DP  - 2017 Apr 13
TI  - Sequence Polymorphism and Intrinsic Structural Disorder as Related to 
      Pathobiological Performance of the Helicobacter pylori CagA Oncoprotein.
LID - 10.3390/toxins9040136 [doi]
LID - 136
AB  - CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally 
      associated with the development of gastrointestinal diseases such as chronic 
      gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric 
      epithelial cells via bacterial type IV secretion, CagA interacts with a number of 
      host proteins through the intrinsically disordered C-terminal tail, which 
      contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA) 
      motif and the CagA multimerization (CM) motif. The EPIYA motif, upon 
      phosphorylation by host kinases, binds and deregulates Src homology 2 
      domain-containing protein tyrosine phosphatase 2 (SHP2), a bona fide oncoprotein, 
      inducing pro-oncogenic mitogenic signaling and abnormal cell morphology. Through 
      the CM motif, CagA inhibits the kinase activity of polarity regulator 
      partitioning-defective 1b (PAR1b), causing junctional and polarity defects while 
      inducing actin cytoskeletal rearrangements. The magnitude of the pathobiological 
      action of individual CagA has been linked to the tandem repeat polymorphisms of 
      these two binding motifs, yet the molecular mechanisms by which they affect 
      disease outcome remain unclear. Recent studies using quantitative techniques have 
      provided new insights into how the sequence polymorphisms in the structurally 
      disordered C-terminal region determine the degree of pro-oncogenic action of CagA 
      in the gastric epithelium.
FAU - Nishikawa, Hiroko
AU  - Nishikawa H
AD  - Division of Microbiology, Graduate School of Medicine, The University of Tokyo, 
      7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. hiroco007@m.u-tokyo.ac.jp.
AD  - CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan. 
      hiroco007@m.u-tokyo.ac.jp.
AD  - Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 
      113-0033, Japan. hiroco007@m.u-tokyo.ac.jp.
FAU - Hatakeyama, Masanori
AU  - Hatakeyama M
AD  - Division of Microbiology, Graduate School of Medicine, The University of Tokyo, 
      7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. mhata@m.u-tokyo.ac.jp.
AD  - CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan. 
      mhata@m.u-tokyo.ac.jp.
AD  - Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 
      113-0033, Japan. mhata@m.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170413
PL  - Switzerland
TA  - Toxins (Basel)
JT  - Toxins
JID - 101530765
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (cagA protein, Helicobacter pylori)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
MH  - Amino Acid Motifs
MH  - Animals
MH  - Antigens, Bacterial/chemistry/*genetics
MH  - Bacterial Proteins/chemistry/*genetics
MH  - Humans
MH  - Oncogene Proteins/chemistry/*genetics
MH  - Polymorphism, Genetic
MH  - Protein Binding/genetics
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism
PMC - PMC5408210
OTO - NOTNLM
OT  - CM motif
OT  - CagA oncoprotein
OT  - CagA polymorphism
OT  - EPIYA motif
OT  - Helicobacter pylori
OT  - gastric carcinoma
OT  - intrinsically disordered region
OT  - scaffold/hub protein
COIS- The authors declare no conflict of interest.
EDAT- 2017/04/14 06:00
MHDA- 2017/08/05 06:00
PMCR- 2017/04/01
CRDT- 2017/04/14 06:00
PHST- 2017/03/01 00:00 [received]
PHST- 2017/04/08 00:00 [revised]
PHST- 2017/04/10 00:00 [accepted]
PHST- 2017/04/14 06:00 [entrez]
PHST- 2017/04/14 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - toxins9040136 [pii]
AID - toxins-09-00136 [pii]
AID - 10.3390/toxins9040136 [doi]
PST - epublish
SO  - Toxins (Basel). 2017 Apr 13;9(4):136. doi: 10.3390/toxins9040136.