HIPPO components mammalian Ste20-like protein kinases 1 and 2 (MST1/2) are well described growth suppressors. However, in pulmonary arterial hypertension (PAH), MST1/2 switch their roles and become pro-proliferative and pro-survival molecules, supporting hyper-proliferation of pulmonary artery (PA) smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs), remodeling of small PAs, and pulmonary hypertension. Here, we report that MST1/2 promotes hyper-proliferation and apoptosis resistance of human PAH PASMCs and PAAFs by up-regulating cell division cycle protein 20 (CDC20), establishing novel link between HIPPO-MST1/2 and cell cycle regulation in PAH. AUTHORS CONTRIBUTIONS: conception and design of the work (EAG, SSP, TVK); acquisition, analysis, and interpretation of data (TD, IZ, LJ, SOO, AP, TA, DL, DG, JRG, PJW, HD, TK); drafting and editing the manuscript (EAG, SSP, TVK, JRG, PJW).
- Dey, T.
- Zhyvylo, I.
- Jiang, L.
- Olapoju, S. O.
- Pena, A.
- Avolio, T.
- Lin, D.
- Goncharov, D.
- Greenland, J. R.
- Wolters, P. J.
- DeLisser, H.
- Pullamsetti, S. S.
- Kudryashova, T. V.
- Goncharova, E. A.
