{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:22:00Z","timestamp":1789456920077,"version":"build-2803163510"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Methionine adenosyltransferase 1A (<jats:italic toggle=\"yes\">MAT1A<\/jats:italic>) is responsible for S\u2010adenosylmethionine (SAMe) biosynthesis in the liver. Mice lacking <jats:italic toggle=\"yes\">Mat1a<\/jats:italic> have hepatic SAMe depletion and develop NASH and HCC spontaneously. Several kinases are activated in <jats:italic toggle=\"yes\">Mat1a<\/jats:italic> knockout (KO) mice livers. However, characterizing the phospho\u2010proteome and determining whether they contribute to liver pathology remain open for study. Our study aimed to provide this knowledge.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We performed phospho\u2010proteomics in <jats:italic toggle=\"yes\">Mat1a<\/jats:italic> KO mice livers with and without SAMe treatment to identify SAMe\u2010dependent changes that may contribute to liver pathology. Our studies used <jats:italic toggle=\"yes\">Mat1a<\/jats:italic> KO mice at different ages treated with and without SAMe, cell lines, in vitro translation and kinase assays, and human liver specimens. We found that the most striking change was hyperphosphorylation and increased content of La\u2010related protein 1 (LARP1), which, in the unphosphorylated form, negatively regulates translation of 5\u2032\u2010terminal oligopyrimidine (TOP)\u2010containing mRNAs. Consistently, multiple TOP proteins are induced in KO livers. Translation of TOP mRNAs ribosomal protein S3 and ribosomal protein L18 was enhanced by <jats:italic toggle=\"yes\">LARP1<\/jats:italic> overexpression in liver cancer cells. We identified LARP1\u2010T449 as a SAMe\u2010sensitive phospho\u2010site of cyclin\u2010dependent kinase 2 (CDK2). Knocking down CDK2 lowered LARP1 phosphorylation and prevented LARP1\u2010overexpression\u2013mediated increase in translation. LARP1\u2010T449 phosphorylation induced global translation, cell growth, migration, invasion, and expression of oncogenic TOP\u2010ribosomal proteins in HCC cells. LARP1 expression is increased in human NASH and HCC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results reveal a SAMe\u2010sensitive mechanism of LARP1 phosphorylation that may be involved in the progression of NASH to HCC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32130","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T14:03:33Z","timestamp":1630073013000},"page":"280-296","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["S\u2010adenosylmethionine inhibits la ribonucleoprotein domain family member 1 in murine liver and human liver cancer cells"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-4603","authenticated-orcid":false,"given":"Komal","family":"Ramani","sequence":"first","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology,Department of Medicine,Cedars\u2010Sinai Medical Center,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-5815","authenticated-orcid":false,"given":"Aaron E.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Genetics,Stanford University School of Medicine,Stanford,California,USA"},{"name":"Smidt Heart Institute and Advanced Clinical Biosystems Research Institute,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-5692","authenticated-orcid":false,"given":"Joshua","family":"Berlind","sequence":"additional","affiliation":[{"name":"Stem Cell Biology and Regenerative Medicine,University of Southern California,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fan","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology,Department of Medicine,Cedars\u2010Sinai Medical Center,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aushinie","family":"Abeynayake","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology,Department of Medicine,Cedars\u2010Sinai Medical Center,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Binek","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute and Advanced Clinical Biosystems Research Institute,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Barbier\u2010Torres","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology,Department of Medicine,Cedars\u2010Sinai Medical Center,Los 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