The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun.
c-Jun is a component of the heterodimeric transcription factor AP-1 that is rapidly activated in response to ultraviolet light (UV). In unstressed cells, c-Jun activity is negatively regulated by transcriptional repressor complexes. Here we show that the F-box protein Fbl10/JHDM1B interacts with c-Jun and represses c-Jun-mediated transcription. Chromatin-immunoprecipitation assays demonstrate that Fbl10 is present at the c-jun promoter, and that c-Jun is required for the recruitment of Fbl10. Fbl10 binds to the unmethylated CpG sequences in the c-jun promoter through the CxxC zinc finger and tethers transcriptional repressor complexes. Suppression of Fbl10 expression by RNA interference (RNAi) induces transcription of c-jun and other c-Jun-target genes, and causes an aberrant cell-cycle progression and increased UV-induced cell death. Furthermore, Fbl10 protein and messenger RNA are downregulated in response to UV in an inverse correlation with c-Jun. Taken together, our results demonstrate that Fbl10 is a key regulator of c-Jun function.
Koyama-Nasu
Ryo
R
Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. ryo.nasu@med.nyu.edu
David
Gregory
G
Tanese
Naoko
N
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic
D044783:F-Box Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human; D010089:Oxidoreductases, N-Demethylating; D048031:JNK Mitogen-Activated Protein Kinases