Regulation of MUC4 expression

Regulation of MUC4 expression. A) Schematic of MUC4 promoter depicting the presence of various transcription factor binding sites AP-1, growth response element (GRE), hepatocyte nuclear factor 1α (HNF1α), STAT, retinoic acid receptor (RAR), SMAD, nuclear factor-κB (κB), retinoid receptor (RXR), and Sp1. The expression of MUC4 can be driven by an active proximal and a distal promoter region. The proximal promoter does not contain a TATA box, while it is present in the distal promoter region. B) Expression of MUC4 is transcriptionally regulated by a variety of growth factors, cytokines, and other components (IFNγ, RA, TGFβ, interleukins, and bile acids). IFNγ-induced expression of MUC4 is mediated by a novel mechanism that involves an up-regulation of STAT1. Retinoic acid-induced expression of MUC4 is mediated by TGFβ2. Induction of MUC4 expression by TGFβ occurs via both SMAD-dependent and -independent pathways. TGFβ-stimulation activates SMAD2/3, which in complex with SMAD4 gets translocated to the nucleus and facilitates the transcription of MUC4. In addition, TGFβ can drive MUC4 expression via MAPK, PI3K, and PKA pathways. Interleukins are known to regulate MUC4 expression via the STAT6 pathway in airway epithelial cells. Bile acids up-regulate MUC4 expression in esophageal cancer cells by involving the HNF1α transcription factor. RBP = retinoic acid binding protein; TCDC = taurochenodeoxycholate; TDC = taurodeoxycholate.

Publication

Structure, evolution, and biology of the MUC4 mucin. () Pallavi Chaturvedi, et al. FASEB J. ;22(4):966-981. Figure: F4. All organisms Drosophila melanogaster Homo sapiens

Disease mentions