Fig. 7: Diagram illustrating the proposed mechanism for the regulatory action of KDM5B-NTT. | Cancer Gene Therapy

Fig. 7: Diagram illustrating the proposed mechanism for the regulatory action of KDM5B-NTT.

From: A truncated and catalytically inactive isoform of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression

Fig. 7

Transcription from Promoter 2 generates NTT mRNAs which include the exon-6, and which lead to the expression of the KDM5B-NTT protein isoform. A second ATG (ATG2) is used for translation of NTT isoform, resulting in a KDM5B N-Terminal Truncated protein isoform including 36 more residues encoded by the exon-6. Even though the NTT mRNAs are around 7% of the total KDM5B transcriptional events, the NTT protein isoform is very much more stable compared to PLU-1, targeted by the proteasome degradation system. NTT chromatin association is driven by the PHD3 domain, which preferentially recognizes the tri-methylated H3K4. This association inhibits the PLU-1 recruitment on common targets and prevents their demethylation, leading to an increase of H3K4me3 levels and resulting in gene derepression. Created with BioRender.com.

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