Bacterial Pathogen Helicobacter pylori: A Bad AKT or Inhibits p53 Protein Activity

摘要: Gastric colonization by Helicobacter pylori is the most prominent known risk factor for gastric cancer. A complex interplay between host and bacterial factors underlies tumorigenic alterations induced bacteria, of which many aspects are not well understood. Recent studies have provided new data regarding regulation protein p53 H. pylori. The interest in originates from its key role tumor suppression, paraphrased scientific literature as “the guardian genome.” Indeed, inactivation strongly associated with an increased susceptibility to numerous tumors animals humans, commonly inactivated during tumorigenesis. Functionally, a transcription that activated response multiple cellular stresses including DNA damage aberrant induction oncogenes. Activated induces target genes, regulate processes such programmed cell death cycle arrest, net effect inhibiting abnormal proliferation promoting cells likely destined development. Since central “life-or-death decision”, activity tightly controlled MDM2 ubiquitin ligase, itself transcriptional p53. ubiquitinates facilitates proteasomal degradation, thus forming regulatory feedback loop. Although infection damages activates oncogenic pathways, bacteria also inhibit [1]. Several demonstrated only enhances mutagenesis P53 gene (TP53) but inhibits mutation-independent manner [1-4]. latter phenomenon less understood may be important early stages tumorigenesis. AKT ERK kinases, enhance degradation [1,3]. Nevertheless, activation alone sufficient degrade fate dependent on levels p14ARF, (Fig. 1). efficiently degrades ARF-deficient cells, whereas halted level infected expressing ARF [5]. Fig. 1 Schema signaling pathways epithelial pylori. In this issue Digestive Diseases Sciences, Xu et al [6] investigated AKT-MDM2-p53 pathway authors first compared expression AKT, phosphorylated (pAKT), MDM2, BAX tissues collected 160 uninfected individuals. specimens were grouped according clinical diagnosis: chronic non-atrophic gastritis (CNAG), metaplastic atrophy (MA), dysplasia (Dys), cancer (GC). Similar previous report Sasaki [7], reported pAKT CNAG patients Notably, correlated significantly protein, indicating potential crosstalk mucosa. Furthermore, was proteins MA Dys, respectively. patients. One aspect addressed study how CagA [1,3,4]. In second part study, using immortalized (GES-1) vitro. This model has plausible advantage over lines, characterized genetic alterations. Another distinction while recapitulated co-culture live chose treat culture filtrates. aforementioned analyses patients’ tissues, treatment filtrates pAKT, Inhibition phosphorylation phosphatidylinositol-3-kinase (LY294002) decreased concomitantly upregulation p53, providing evidence through AKT-MDM2 signaling. speculated determined balance Although it explored another possibility upregulated via inhibition p14ARF been previously [5]. The cytostatic cytotoxic effects inducing damage, G1/S arrest apoptosis. Interestingly, viability further reduced after MDM2. Reduced survival - [8]. These seemingly opposing results reveal diverse could often reconciled differences experimental models An interesting example recent Wroblewski al, who strains growth induce organoids [9]. In summary, methodically advanced field – signaling, opening up opportunities better understanding host-bacterial interactions potential.