Delgado Inês L S, Carmona Bruno, Nolasco Sofia, Santos Dulce, Leitão Alexandre, Soares Helena
CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, 1749-024 Lisboa, Portugal.
Biology (Basel). 2020 Nov 24;9(12):413. doi: 10.3390/biology9120413.
The MOB family proteins are constituted by highly conserved eukaryote kinase signal adaptors that are often essential both for cell and organism survival. Historically, MOB family proteins have been described as kinase activators participating in Hippo and Mitotic Exit Network/ Septation Initiation Network (MEN/SIN) signaling pathways that have central roles in regulating cytokinesis, cell polarity, cell proliferation and cell fate to control organ growth and regeneration. In metazoans, MOB proteins act as central signal adaptors of the core kinase module MST1/2, LATS1/2, and NDR1/2 kinases that phosphorylate the YAP/TAZ transcriptional co-activators, effectors of the Hippo signaling pathway. More recently, MOBs have been shown to also have non-kinase partners and to be involved in cilia biology, indicating that its activity and regulation is more diverse than expected. In this review, we explore the possible ancestral role of MEN/SIN pathways on the built-in nature of a more complex and functionally expanded Hippo pathway, by focusing on the most conserved components of these pathways, the MOB proteins. We discuss the current knowledge of MOBs-regulated signaling, with emphasis on its evolutionary history and role in morphogenesis, cytokinesis, and cell polarity from unicellular to multicellular organisms.
MOB家族蛋白由高度保守的真核生物激酶信号适配器组成，这些适配器对于细胞和生物体的存活通常至关重要。从历史上看，MOB家族蛋白被描述为参与Hippo和有丝分裂退出网络/隔膜起始网络（MEN/SIN）信号通路的激酶激活剂，这些信号通路在调节胞质分裂、细胞极性、细胞增殖和细胞命运以控制器官生长和再生方面发挥着核心作用。在多细胞动物中，MOB蛋白作为核心激酶模块MST1/2、LATS1/2和NDR1/2激酶的中心信号适配器，这些激酶使YAP/TAZ转录共激活因子磷酸化，YAP/TAZ是Hippo信号通路的效应器。最近，MOB蛋白已被证明还具有非激酶伴侣，并参与纤毛生物学，这表明其活性和调节比预期的更加多样化。在这篇综述中，我们通过关注这些信号通路中最保守的成分——MOB蛋白，探讨了MEN/SIN信号通路在更复杂且功能扩展的Hippo信号通路的内在本质上可能具有的祖先作用。我们讨论了目前关于MOB调节信号的知识，重点是其进化历史以及在从单细胞生物到多细胞生物的形态发生、胞质分裂和细胞极性中的作用。
