The RCAN1 inhibits NF-κB and suppresses lymphoma growth in mice.
Nuclear factor-κB (NF-κB) has a vital role in cell survival. Inhibition of NF-κB has been proven to be an efficient therapeutic pathway for various cancers. Activation of NF-κB is mainly through serine residues' phosphorylation of inhibitor of κBα (IκBα) by IKK complex. Phosphorylation at tyrosine 42 is an alternative pathway in regulation of IκBα and NF-κB signaling, though little is known about the underlying mechanism. Here we identified regulator of calcineurin 1 (RCAN1) as a novel endogenous inhibitor of NF-κB signaling pathway. RCAN1 can interact with IκBα and affect the phosphorylation of IκBα at tyrosine 42. Overexpression of RCAN1 by adenovirus reduced cell viability in lymphoma Raji cells and restrained the growth of lymphoma transplants in mice. We further found that N terminus 1-103aa of RCAN1 is sufficient to inhibit NF-κB and reduce cell viability of lymphoma cells. Our study implicated a novel therapeutic approach for lymphoma by RCAN1 through inhibition of NF-κB signaling.
Brain Research Institute, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
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Liu
Brain Research Institute, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
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Zheng
Brain Research Institute, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
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Wang
Department of Hematology, Weifang People's Hospital, 151 Guangwen Street, Weifang 261041, China.
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Ran
Brain Research Institute, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
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Liu
Brain Research Institute, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
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X
Sun
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D016513:Mice, SCID; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C108612:RCAN1 protein, human; D025521:Tumor Suppressor Proteins; D000072000:NF-KappaB Inhibitor alpha; D019703:Calcineurin