| First Author | Lee EJ | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 46 | Pages | 29001-29012 |
| PubMed ID | 33122431 | Mgi Jnum | J:298801 |
| Mgi Id | MGI:6477498 | Doi | 10.1073/pnas.2009334117 |
| Citation | Lee EJ, et al. (2020) TAZ/Wnt-beta-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A 117(46):29001-29012 |
| abstractText | Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. The Hippo signaling pathway regulates organ growth and cell proliferation. Herein, we demonstrate the regulatory mechanism of cystogenesis in ADPKD by transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo signaling effector. TAZ was highly expressed around the renal cyst-lining epithelial cells of Pkd1-deficient mice. Loss of Taz in Pkd1-deficient mice reduced cyst formation. In wild type, TAZ interacted with PKD1, which inactivated beta-catenin. In contrast, in PKD1-deficient cells, TAZ interacted with AXIN1, thus increasing beta-catenin activity. Interaction of TAZ with AXIN1 in PKD1-deficient cells resulted in nuclear accumulation of TAZ together with beta-catenin, which up-regulated c-MYC expression. Our findings suggest that the PKD1-TAZ-Wnt-beta-catenin-c-MYC signaling axis plays a critical role in cystogenesis and might be a potential therapeutic target against ADPKD. |
