biostudies-literatureUnknown33(17)Tsuchiya YImpairment of the ubiquitin-proteasome system (UPS) has been implicated in the pathogenesis of human diseases, including neurodegenerative disorders. Thus, stimulating proteasome activity is a promising strategy to ameliorate these age-related diseases. Here we show that the protein kinase casein kinase 2 (CK2) regulates the transcriptional activity of Nrf1 to control the expression of the proteasome genes and thus the clearance of ubiquitinated proteins. We identify CK2 as an Nrf1-binding protein and find that the knockdown of CK2 enhances the Nrf1-dependent expression of the proteasome subunit genes. Real-time monitoring of proteasome activity reveals that CK2 knockdown alleviates the accumulation of ubiquitinated proteins upon proteasome inhibition. Furthermore, we identify Ser 497 of NMolecular and cellular biology3461-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC3753846biostudies-literatureThe casein kinase 2-nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression.PMC3753846Ito TOkamuro SIto YNishida EFukagai KTsuchiya YMorita TOhtake NNatsume TKobayashi AKarim MRIemura STaniguchi HfalseThe casein kinase 2-nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression.Impairment of the ubiquitin-proteasome system (UPS) has been implicated in the pathogenesis of human diseases, including neurodegenerative disorders. Thus, stimulating proteasome activity is a promising strategy to ameliorate these age-related diseases. Here we show that the protein kinase casein kinase 2 (CK2) regulates the transcriptional activity of Nrf1 to control the expression of the proteasome genes and thus the clearance of ubiquitinated proteins. We identify CK2 as an Nrf1-binding protein and find that the knockdown of CK2 enhances the Nrf1-dependent expression of the proteasome subunit genes. Real-time monitoring of proteasome activity reveals that CK2 knockdown alleviates the accumulation of ubiquitinated proteins upon proteasome inhibition. Furthermore, we identify Ser 497 of N2013-01-01T00:00:00Z2013 Sep2025-04-04T22:06:39.345Z2019-03-27T01:15:06ZS-EPMC37538462381688110.1128/MCB.01271-1210.1128/mcb.01271-12