The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun

• Published in: Nature cell biology Vol. 9; no. 9; pp. 1074 - 1080
• Main Authors: David, Gregory, Koyama-Nasu, Ryo, Tanese, Naoko
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2007
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Cell Line; F-Box Proteins - genetics; F-Box Proteins - metabolism; Gene Expression Regulation, Enzymologic; Genetic transcription; Humans; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Jumonji Domain-Containing Histone Demethylases; Molecular Sequence Data; Oxidoreductases, N-Demethylating - genetics; Oxidoreductases, N-Demethylating - metabolism; Physiological aspects; Polymerase chain reaction; Promoter Regions, Genetic; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA Interference; Sequence Alignment; Transcription factors; Transcription, Genetic; Ultraviolet radiation; Zinc finger proteins; United States; New York; United States > US
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1628

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.