Table 1.
Summary of the Various Signaling Pathways Involving Menin From Upstream Extracellular Signals to Menin-Binding Partners, Mechanism of Action, and Functional Outcome as a Result
| Organ | Disease | Signaling | Menin Binding Partners | Mechanism | Outcome |
|---|---|---|---|---|---|
| Parathyroid/pituitary | Normal | TGF-β | Smad3 | ? | Inhibit proliferation |
| Liver | HCC/cirrhosis | TGF-β | Smad3 | ? | COL1α2 expression, fibrosis, activated HSCs |
| Liver | HCC | ? | ? | H3K4me3 | YAP transcription |
| Liver/fibroblast | Normal | ? | JunD | HDAC | Cyclin D1 repression |
| Liver | Normal | TNF-α | JunD/NF-κb subunits | HDAC | Cell survival: increased TIMP, IL-6, and MMP-9 expression. Decreased p53/p27 expression |
| Liver/stellate cells | MDR2−/− | Vitamin D | VDR | ? | Decreased fibrosis/HSC activation |
| Liver | HCC | NF-κβ | P65 | ? | Decreased transcription/growth |
| Liver | Steatosis | ? | PPARα | ? | Fatty acid oxidation |
| Liver | Steatosis | ? | Sirt1 | HDAC | Loss of CD36 (fatty acid oxidation) |
| Pancreas islets | Diabetes | Progesterone/prolactin | ? | ? | Decreased growth/increased growth |
| Pancreas | PNET | ? | MLL | H3K4 | p27/18, HOX loci expression. Decreased islet proliferation |
| Pancreas | Normal | Wnt | β-Catenin/TCF | H3K4me3 | AXIN2 expression/inhibit proliferation |
| Pancreas | MEN1 syndrome | Estrogen | ER/menin | H3K4me3 | TFF1 expression/survival |
The left two columns specify the organ and disease state. ? indicates that particular signaling aspect in relation to menin pathways remains to be elucidated.