ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/077/SRR10315777/SRR10315777_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/079/SRR10315779/SRR10315779_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/075/SRR10315775/SRR10315775_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/071/SRR10315771/SRR10315771_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/072/SRR10315772/SRR10315772_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/078/SRR10315778/SRR10315778_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/073/SRR10315773/SRR10315773_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/079/SRR10315779/SRR10315779_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/076/SRR10315776/SRR10315776_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/078/SRR10315778/SRR10315778_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/076/SRR10315776/SRR10315776_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/072/SRR10315772/SRR10315772_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/074/SRR10315774/SRR10315774_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/080/SRR10315780/SRR10315780_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/075/SRR10315775/SRR10315775_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/077/SRR10315777/SRR10315777_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/080/SRR10315780/SRR10315780_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/071/SRR10315771/SRR10315771_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/074/SRR10315774/SRR10315774_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR103/073/SRR10315773/SRR10315773_1.fastq.gzprimaryOK200GenomicsMajor Lab, Department of Cell Biology and Physiology Department of Otolaryngology, Washington University in St. Louishttps://www.ebi.ac.uk/ena/browser/view/PRJNA578614Homo sapiensWe found that the understudied Brain Specific Kinase 2 and 1 (BRSK2/1) proteins suppress NRF2-dependent transcription and NRF2 protein levels in a kinase-dependent fashion. Integrative phosphoproteomic screens, RNAseq profiling and follow-up validation studies revealed BRSK2/1-driven activation of AMPK and suppression of MTOR signaling. BRSK2 over-expression suppressed global protein synthesis and decreased ribosome-RNA associations, which results in decreased NRF2 protein levels. Overall, our data establish the BRSK1 and BRSK2 kinases as negative regulators of NRF2 via the AMPK/MTOR signaling axis. Overall design: Evaluation of BRSK2/1 induced changes in RNA via overexpression in HEK293Ts.ENACG13826, RNA polymerase II core promoter proximal region sequence-specific binding, T-cell leukemia, anon-WO0153538.7, anon-WO0153538.6, AGL4, C11orf7, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, SEPALLATA 2, Gm1100, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Transcription Factor, SAD1, l(3)j5E7, l(3)03921, NRF2A, transcription factor activity, BcDNA:RE05559, zinc ion regulated core promoter proximal region sequence-specific DNA binding, E4TF1-60, Dmel_CG13826, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, 4833424K13Rik, CG4566, RNA polymerase II transcription factor activity, NFT2, CG43286, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, CNC, Cnc, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, CG17894, DmelCG43286, F14P3.4, hSAD1, Transcription, Factors, copper ion regulated core promoter proximal region sequence-specific binding., F14P3_4, CG4578, F10N7_150, NRF2, CNC_DROME, Nrf2, RCH04A07, metal ion regulated core promoter proximal region sequence-specific binding, SAD-A, SAD-B, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription factor, F10N7.150, AI194320, 5134, STK29, SADB, RNA polymerase II proximal promoter sequence-specific DNA binding, SADA, copper ion regulated proximal promoter sequence-specific DNA binding, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, AGAMOUS-like 4, E4TF1A, Dmel_CG17894, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, metal ion regulated sequence-specific DNA binding, PEN11B, metal ion regulated proximal promoter sequence-specific DNA binding, TRANSCRIPTION FACTOR, RNA polymerase II distal enhancer sequence-specific bindingCG13826, RNA polymerase II core promoter proximal region sequence-specific binding, T-cell leukemia, anon-WO0153538.7, anon-WO0153538.6, AGL4, C11orf7, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, SEPALLATA 2, Gm1100, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Transcription Factor, SAD1, l(3)j5E7, l(3)03921, NRF2A, transcription factor activity, BcDNA:RE05559, zinc ion regulated core promoter proximal region sequence-specific DNA binding, E4TF1-60, Dmel_CG13826, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, 4833424K13Rik, CG4566, RNA polymerase II transcription factor activity, NFT2, CG43286, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, CNC, Cnc, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, CG17894, DmelCG43286, F14P3.4, hSAD1, Transcription, Factors, copper ion regulated core promoter proximal region sequence-specific binding., F14P3_4, CG4578, F10N7_150, NRF2, CNC_DROME, Nrf2, RCH04A07, metal ion regulated core promoter proximal region sequence-specific binding, SAD-A, SAD-B, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription factor, F10N7.150, AI194320, 5134, STK29, SADB, RNA polymerase II proximal promoter sequence-specific DNA binding, SADA, copper ion regulated proximal promoter sequence-specific DNA binding, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, AGAMOUS-like 4, E4TF1A, Dmel_CG17894, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, metal ion regulated sequence-specific DNA binding, PEN11B, metal ion regulated proximal promoter sequence-specific DNA binding, TRANSCRIPTION FACTOR, RNA polymerase II distal enhancer sequence-specific bindingfalseMolecular characterization of BRSK2 and BRSK1 kinases as negative regulators of the NRF2 transcription factorMolecular characterization of BRSK2 and BRSK1 kinases as negative regulators of the NRF2 transcription factor2025-09-242019-11-19PRJNA578614GSE1391359606