{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:45:04Z","timestamp":1790369104036,"version":"4.1.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 138833"],"award-info":[{"award-number":["R01 138833"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 206564"],"award-info":[{"award-number":["R01 206564"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["P01 CA268991"],"award-info":[{"award-number":["P01 CA268991"]}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX002115"],"award-info":[{"award-number":["BX002115"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018896","name":"Sylvester Comprehensive Cancer Center, University of Miami Health Systems","doi-asserted-by":"publisher","award":["P30CA24013"],"award-info":[{"award-number":["P30CA24013"]}],"id":[{"id":"10.13039\/100018896","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    ) is a common gastric pathogen that infects approximately half of the world\u2019s population. Infection with\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    can lead to diverse pathological conditions, including chronic gastritis, peptic ulcer disease, and cancer. The latter is the most severe consequence of\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    infection. According to epidemiological studies, gastric infection with\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    is the strongest known risk factor for non-cardia gastric cancer (GC), which remains one of the leading causes of cancer-related deaths worldwide. However, it still remains to be poorly understood how host-microbe interactions result in cancer development in the human stomach. Here we focus on the\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    bacterial factors that affect the host ubiquitin proteasome system. We investigated E3 ubiquitin ligases SIVA1 and ULF that regulate p14ARF (p19ARF in mice) tumor suppressor. ARF plays a key role in regulation of the oncogenic stress response and is frequently inhibited during GC progression. Expression of ARF, SIVA1 and ULF proteins were investigated in gastroids,\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    -infected mice and human gastric tissues. The role of the\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    type IV secretion system was assessed using various\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    isogenic mutants. Our studies demonstrated that\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>pylori<\/jats:italic>\n                    infection results in induction of ULF, decrease in SIVA1 protein levels, and subsequent ubiquitination and degradation of p14ARF tumor suppressor. Bacterial CagA protein was found to sequentially bind to SIVA1 and ULF proteins. This process is regulated by CagA protein phosphorylation at the EPIYA motifs. Downregulation of ARF protein leads to inhibition of cellular apoptosis and oncogenic stress response that may promote gastric carcinogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010628","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T13:37:47Z","timestamp":1656509867000},"page":"e1010628","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Helicobacter pylori pathogen inhibits cellular responses to oncogenic stress and apoptosis"],"prefix":"10.1371","volume":"18","author":[{"given":"Manikandan","family":"Palrasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Zaika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodisundaram","family":"Paulrasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindran","family":"Caspa Gokulan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Suarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Que","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"El-Rifai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Peek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Garcia-Buitrago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6760-2020","authenticated-orcid":true,"given":"Alexander I.","family":"Zaika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"issue":"3","key":"ppat.1010628.ref001","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin."},{"issue":"8","key":"ppat.1010628.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13081878","article-title":"Role of Bacterial and Viral Pathogens in Gastric Carcinogenesis.","volume":"13","author":"M Palrasu","year":"2021","journal-title":"Cancers (Basel)."},{"issue":"3","key":"ppat.1010628.ref003","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1073\/pnas.0711183105","article-title":"Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse","volume":"105","author":"N Ohnishi","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ppat.1010628.ref004","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cell.2007.07.003","article-title":"Cellular senescence in cancer and aging","volume":"130","author":"M 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