TY - JOUR T1 - Endoplazmik retikulum-aracılı protein yıkım yolağında görev yapan p97/VCP ve Ufd1-Npl4 adlı proteinlerin NF-κB yolağına etkisinin prostat kanser hücre hattında incelenmesi TT - Investigating the effect of p97/VCP and Ufd1-Npl4 proteins functioning in the endoplasmic reticulum-associated degradation on the NF-κB pathway AU - Ballar Kırmızıbayrak, Petek AU - Erbaykent Tepedelen, Burcu PY - 2018 DA - September DO - 10.19161/etd.418150 JF - Ege Tıp Dergisi JO - EJM PB - Ege Üniversitesi WT - DergiPark SN - 1016-9113 SP - 142 EP - 146 VL - 57 IS - 3 LA - tr AB - Amaç: Bu çalışmada, endoplazmik retikulum-aracılı yıkım yolağındakiretrotranslokasyon basamağının anahtar proteini olan p97/VCP ve etkileşimpartnerleri olan Ufd1 ve Npl4 proteinlerinin NF-κB yolağı üzerine etkileriprostat kanser hücre hattında incelendi.Gereç veYöntem: p97/VCP, Ufd1 ve Npl4 ifadeleri RNA interferans RNAi(RNA interferans) teknolojisi ile LNCAP hücrelerinde susturuldu ve NF-κBaktivitesi ikili lusiferaz yöntemi ile NF-κB yolağı proteinlerinin ifadesi iseimmünoblotlama ile değerlendirildi.Bulgular: p97/VCP, Ufd1 ve Npl4 ifadelerinin susturulması LNCaP hücrelerinde NF-κBaktivitesini anlamlı olarak azaltmış ve IκBα protein seviyesini arttırırkenfosforile NF-κB ve fosforile IκBα seviyelerini azaltmıştır.Sonuç: Retrotranslokasyon kompleks üyelerinin susturulması ile LNCaPhücrelerinde NF-κB aktivitesinin azalmasının NF-κB inhibitörü olan IκBαseviyesinin artmasına bağlı olduğu düşünülmektedir. Bulgularımız p97/VCP veetkileşim partnerleri Ufd1-Npl4 proteinlerinin prostat kanserinde NF-κByolağının düzenlenmesinde önemli bir etken olabileceğini önermektedir. KW - Endoplazmik retikulum ilişkili yıkım yolağı KW - retrotranslokasyon KW - p97/VCP KW - NF-κB KW - prostat kanseri. N2 - Aim: In this study, the effects of p97/VCP and itsinteracting partners Ufd1 and Npl4 proteins, which function at theretrotranslocation step of endoplasmic reticulum-associated degradation wereinvestigated on the NF-κB pathway in the prostate cancer cell line.Materials and Methods: The expressions of p97/VCP,Ufd1 and Npl4 were silenced in LNCaP cells using RNAi (RNA interference)technology. NF-κB activity was evaluated by dual luciferase assay system andtheexpressionof NF-κB pathway proteins were investigated using immunoblotting.Results: Silencing of expression of p97/VCP, Ufd1 and Npl4significantly diminished NF-κB activity and increased the level of IκBα proteinwhile decreased phosphorylated NF-κB and phosphorylated IκBα levels in LNCaPcells.Conclusion: The decrease NF-κB activityupon silencing the expressions of retrotranslocation complex members in LNCaPcells might be associated with the increased level of NF-κB inhibitor IκBα. Ourdata suggests that p97/VCP and its interacting partners might be importantfactors on the regulation of NF-κB pathway in the prostate cancer. CR - Ahner A, Brodsky JL. Checkpoints in ER-associated degradation: Excuse me, which way to the proteasome? Trends Cell Biol 2004;14(9):474-8. CR - Meusser B, Hirsch C, Jarosch E, Sommer T. ERAD: The long road to destruction. Nat Cell Biol 2005;7(8):766-72. CR - Hartl FU, Hayer-Hartl M. 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