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.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Line, F-Box Proteins, Gene Expression Regulation, Enzymologic, Humans, JNK Mitogen-Activated Protein Kinases, Jumonji Domain-Containing Histone Demethylases, Molecular Sequence Data, Oxidoreductases, N-Demethylating, Promoter Regions, Genetic, Protein Isoforms, RNA Interference, Recombinant Fusion Proteins, Sequence Alignment, Transcription, Genetic
Nat. Cell Biol.
Date: Sep. 01, 2007
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