The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNA-Induced Silencing of NF-κB–Inducing Kinase
Identifieur interne : 000D64 ( Ncbi/Curation ); précédent : 000D63; suivant : 000D65The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNA-Induced Silencing of NF-κB–Inducing Kinase
Auteurs : Hanbit Jang [Corée du Sud] ; Seulki Park [Corée du Sud] ; Jaehoon Kim [Corée du Sud] ; Jong Hwan Kim [Corée du Sud] ; Seon-Young Kim [Corée du Sud] ; Sayeon Cho [Corée du Sud] ; Sung Goo Park [Corée du Sud] ; Byoung Chul Park [Corée du Sud] ; Sunhong Kim [Corée du Sud] ; Jeong-Hoon Kim [Corée du Sud]Source :
- Molecules and Cells [ 1016-8478 ] ; 2019.
Abstract
NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB–inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the
Url:
DOI: 10.14348/molcells.2019.0239
PubMed: 31870133
PubMed Central: 6999715
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Seulki" sort="Park, Seulki" uniqKey="Park S" first="Seulki" last="Park">Seulki Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jaehoon" sort="Kim, Jaehoon" uniqKey="Kim J" first="Jaehoon" last="Kim">Jaehoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-molce-43-023">Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jong Hwan" sort="Kim, Jong Hwan" uniqKey="Kim J" first="Jong Hwan" last="Kim">Jong Hwan Kim</name><affiliation wicri:level="1"><nlm:aff id="af6-molce-43-023">Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Seon Young" sort="Kim, Seon Young" uniqKey="Kim S" first="Seon-Young" last="Kim">Seon-Young Kim</name><affiliation wicri:level="1"><nlm:aff id="af6-molce-43-023">Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Sayeon" sort="Cho, Sayeon" uniqKey="Cho S" first="Sayeon" last="Cho">Sayeon Cho</name><affiliation wicri:level="1"><nlm:aff id="af7-molce-43-023">College of Pharmacy, Chung-Ang University, Seoul 06974,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Sung Goo" sort="Park, Sung Goo" uniqKey="Park S" first="Sung Goo" last="Park">Sung Goo Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Byoung Chul" sort="Park, Byoung Chul" uniqKey="Park B" first="Byoung Chul" last="Park">Byoung Chul Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-molce-43-023">Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Sunhong" sort="Kim, Sunhong" uniqKey="Kim S" first="Sunhong" last="Kim">Sunhong Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-molce-43-023">Department of Bio-Molecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jeong Hoon" sort="Kim, Jeong Hoon" uniqKey="Kim J" first="Jeong-Hoon" last="Kim">Jeong-Hoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31870133</idno><idno type="pmc">6999715</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999715</idno><idno type="RBID">PMC:6999715</idno><idno type="doi">10.14348/molcells.2019.0239</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000703</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000703</idno><idno type="wicri:Area/Pmc/Curation">000703</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000703</idno><idno type="wicri:Area/Pmc/Checkpoint">000316</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000316</idno><idno type="wicri:Area/Ncbi/Merge">000D64</idno><idno type="wicri:Area/Ncbi/Curation">000D64</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNA-Induced Silencing of NF-κB–Inducing Kinase</title><author><name sortKey="Jang, Hanbit" sort="Jang, Hanbit" uniqKey="Jang H" first="Hanbit" last="Jang">Hanbit Jang</name><affiliation wicri:level="1"><nlm:aff id="af1-molce-43-023">Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Seulki" sort="Park, Seulki" uniqKey="Park S" first="Seulki" last="Park">Seulki Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jaehoon" sort="Kim, Jaehoon" uniqKey="Kim J" first="Jaehoon" last="Kim">Jaehoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-molce-43-023">Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jong Hwan" sort="Kim, Jong Hwan" uniqKey="Kim J" first="Jong Hwan" last="Kim">Jong Hwan Kim</name><affiliation wicri:level="1"><nlm:aff id="af6-molce-43-023">Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Seon Young" sort="Kim, Seon Young" uniqKey="Kim S" first="Seon-Young" last="Kim">Seon-Young Kim</name><affiliation wicri:level="1"><nlm:aff id="af6-molce-43-023">Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Sayeon" sort="Cho, Sayeon" uniqKey="Cho S" first="Sayeon" last="Cho">Sayeon Cho</name><affiliation wicri:level="1"><nlm:aff id="af7-molce-43-023">College of Pharmacy, Chung-Ang University, Seoul 06974,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Sung Goo" sort="Park, Sung Goo" uniqKey="Park S" first="Sung Goo" last="Park">Sung Goo Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Byoung Chul" sort="Park, Byoung Chul" uniqKey="Park B" first="Byoung Chul" last="Park">Byoung Chul Park</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4-molce-43-023">Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Sunhong" sort="Kim, Sunhong" uniqKey="Kim S" first="Sunhong" last="Kim">Sunhong Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-molce-43-023">Department of Bio-Molecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Jeong Hoon" sort="Kim, Jeong Hoon" uniqKey="Kim J" first="Jeong-Hoon" last="Kim">Jeong-Hoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-molce-43-023">Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molce-43-023">Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecules and Cells</title><idno type="ISSN">1016-8478</idno><idno type="eISSN">0219-1032</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB–inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the <italic>TP53</italic> gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Balaji, S" uniqKey="Balaji S">S. Balaji</name></author><author><name sortKey="Ahmed, M" uniqKey="Ahmed M">M. Ahmed</name></author><author><name sortKey="Lorence, E" uniqKey="Lorence E">E. Lorence</name></author><author><name sortKey="Yan, F" uniqKey="Yan F">F. Yan</name></author><author><name sortKey="Nomie, K" uniqKey="Nomie K">K. Nomie</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartel, D P" uniqKey="Bartel D">D.P. Bartel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beg, M S" uniqKey="Beg M">M.S. 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