Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, USA.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA.
Cell Mol Life Sci. 2021 Mar;78(5):1943-1955. doi: 10.1007/s00018-020-03690-w. Epub 2020 Nov 3.
The Hippo signal transduction pathway is an essential regulator of organ size during developmental growth by controlling multiple cellular processes such as cell proliferation, cell death, differentiation, and stemness. Dysfunctional Hippo signaling pathway leads to dramatic tissue overgrowth. Here, we will briefly introduce the Hippo tumor suppressor pathway before focusing on one of its members and the unexpected twists that followed our quest of its functions in its multifarious actions beside the Hippo pathway: the STK38 kinase. In this review, we will precisely discuss the newly identified role of STK38 on regulating the nuclear export machinery by phosphorylating and activating, the major nuclear export receptor XPO1. Finally, we will phrase STK38's role on regulating the subcellular distribution of crucial cellular regulators such as Beclin1 and YAP1 with its implication in cancer.
Hippo 信号转导通路通过控制细胞增殖、细胞死亡、分化和干细胞特性等多种细胞过程,是发育生长过程中器官大小的重要调节因子。Hippo 信号通路功能失调会导致组织过度生长。在这里,我们将简要介绍 Hippo 肿瘤抑制通路,然后重点介绍其成员之一,以及在 Hippo 通路之外,其在多种作用中功能的意想不到的转变:STK38 激酶。在这篇综述中,我们将详细讨论 STK38 通过磷酸化和激活主要核输出受体 XPO1 来调节核输出机制的新功能。最后,我们将描述 STK38 通过调节 Beclin1 和 YAP1 等关键细胞调节剂的亚细胞分布在癌症中的作用。