{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:39:30Z","timestamp":1790743170453,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,3,31]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The role of\n                    <jats:italic>FLCN<\/jats:italic>\n                    as a tumor suppressor in kidney cancer has been well documented, whereas the functional roles of folliculin (FLCN)-interacting proteins 1 and 2 (FNIP1 and FNIP2) in kidney are unknown. In this study, we demonstrate that double inactivation of\n                    <jats:italic>Fnip1<\/jats:italic>\n                    and\n                    <jats:italic>Fnip2<\/jats:italic>\n                    leads to enlarged polycystic kidneys or kidney cancer, which mimics the phenotypes seen in\n                    <jats:italic>Flcn<\/jats:italic>\n                    -deficient kidneys and underscores the significance of Fnip1 and Fnip2 in kidney tumor suppression. Moreover, we found that\n                    <jats:italic>Fnip1\/Fnip2<\/jats:italic>\n                    mRNA ratios differ among organs, which may reflect tissue-specific roles for each\n                    <jats:italic>Fnip<\/jats:italic>\n                    . Our findings define Fnip1 and Fnip2 as critical components of the Flcn complex that are essential for its tumor suppressive function and will aid in the development of novel therapeutics for kidney cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1419502112","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T22:56:33Z","timestamp":1426546593000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn"],"prefix":"10.1073","volume":"112","author":[{"given":"Hisashi","family":"Hasumi","sequence":"first","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"Departments of bUrology and Molecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Baba","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"International Research Center for Medical Sciences, Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hasumi","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lang","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HyoungBin F.","family":"Oh","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Radiation Biology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Merino","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yao","sequence":"additional","affiliation":[{"name":"Departments of bUrology and Molecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ito","sequence":"additional","affiliation":[{"name":"Departments of bUrology and Molecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Furuya","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Yokohama City University, Yokohama 236-0004, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Iribe","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Yokohama City University, Yokohama 236-0004, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Kodama","sequence":"additional","affiliation":[{"name":"Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Southon","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and"},{"name":"Laboratory of Animal Sciences Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Tessarollo","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Electron Microscope Laboratory, Cancer Technology Group,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana C.","family":"Haines","sequence":"additional","affiliation":[{"name":"Veterinary Pathology Section, Pathology\/Histotechnology Laboratory, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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