Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, NSW, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, NSW, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Cell Signal. 2021 Feb;78:109868. doi: 10.1016/j.cellsig.2020.109868. Epub 2020 Dec 1.
Tristetraprolin (TTP) is a destabilizing mRNA binding protein known to regulate gene expression of a wide variety of targets, including those that control inflammation. TTP expression, regulation and function is controlled by phosphorylation. While the importance of key serine (S) sites (S and S in mice and S in humans) has been recognized, other sites on the hyperphosphorylated TTP protein have more recently emerged as playing an important role in regulating cellular signalling and downstream functions of TTP. In order to propel investigation of TTP and fully exploit its potential as a drug target in inflammatory disease, this review will catalogue TTP phosphorylation sites in both the murine and human TTP protein, the known and unknown roles and functions of these sites, the kinases and phosphatases that act upon TTP and overview methodological approaches to increase our knowledge of this important protein regulated by phosphorylation.
Tristetraprolin(TTP)是一种不稳定的 mRNA 结合蛋白,已知可调节多种靶基因的表达,包括控制炎症的靶基因。TTP 的表达、调节和功能受磷酸化控制。虽然关键丝氨酸(S)位点(小鼠中的 S 和 S 以及人类中的 S)的重要性已得到认可,但 TTP 蛋白的其他高度磷酸化位点最近已被证明在调节细胞信号转导和 TTP 的下游功能方面发挥着重要作用。为了推动 TTP 的研究,并充分利用其作为炎症性疾病药物靶点的潜力,本综述将对鼠和人 TTP 蛋白中的 TTP 磷酸化位点进行分类,这些位点的已知和未知作用和功能,作用于 TTP 的激酶和磷酸酶,并概述增加对这种受磷酸化调节的重要蛋白质的了解的方法学方法。