Li Jing, Urabe Go, Huang Yitao, Zhang Mengxue, Wang Bowen, Marcho Lynn, Shen Hongtao, Kent K Craig, Guo Lian-Wang
Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Cellular and Molecular Pathology Graduate Program, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
JACC Basic Transl Sci. 2021 Mar 22;6(3):257-283. doi: 10.1016/j.jacbts.2020.12.015. eCollection 2021 Mar.
Polo-like kinase 4 (PLK4) is canonically known for its cytoplasmic function in centriole duplication. Here we show a noncanonical PLK4 function of regulating the transcription factor SRF's nuclear activity and associated myofibroblast-like cell-type transition. In this context, we have further found that PLK4's phosphorylation and transcription are respectively regulated by PDGF receptor and epigenetic factor BRD4. Furthermore, in vivo experiments suggest PLK4 inhibition as a potential approach to mitigating vascular fibrosis.
Polo样激酶4（PLK4）通常因其在中心粒复制中的细胞质功能而为人所知。在此，我们展示了PLK4的一种非经典功能，即调节转录因子血清反应因子（SRF）的核活性以及相关的肌成纤维细胞样细胞类型转变。在这种情况下，我们进一步发现PLK4的磷酸化和转录分别受血小板衍生生长因子受体（PDGF受体）和表观遗传因子BRD4的调节。此外，体内实验表明抑制PLK4是减轻血管纤维化的一种潜在方法。
