MOB1 was first identified in yeast as a protein that binds to Mps with essential roles in the completion of mitosis and the maintenance of ploidy (1). Its Drosophila and mammalian homologs, Mats and MOB1, respectively, are involved in the Hippo signaling tumor suppressor pathway, which plays a critical role in organ size regulation and which has been implicated in cancer development (2-5). There are two MOB1 proteins in humans, MOB1A and MOB1B, that are encoded by two different genes but which have greater than 95% amino acid sequence identity (6). Both forms bind to members of the nuclear Dbf2-related (NDR) kinases, such as LATS1/2 and NDR1/2, thereby stimulating kinase activity (7-9). This binding is promoted by the phosphorylation of MOB1 at several threonine residues (e.g., Thr12, Thr35) by MST1 and/or MST2 (5,10).Phosphorylation at Thr35 by MST1/2 stabilizes MOB1, enhancing its binding and regulation of LATS1 (5). The resultant increase in LATS1 kinase activity promotes inhibitory phosphorylation of the transcriptional co-activators YAP and TAZ (11,12), leading to changes in the expression of genes involved in cell cycle progression (13).
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