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Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View

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Specialty Cell Biology
Date 2021 Apr 19
PMID 33869224
Citations 20
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Abstract

Initially identified in , the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Many upstream signals, including cell adhesion, polarity, mechanical stress, and soluble factors, regulate Hippo signaling through the kinase cascade, leading to change in the cytoplasmic/nuclear localization of Yki/YAP/Taz. However, recent studies have uncovered other mechanisms that regulate Yki/YAP/Taz subcellular localization, stability, and activity independent of the Hpo kinase cascade. These mechanisms provide additional layers of pathway regulation, nodes for pathway crosstalk, and opportunities for pathway intervention in cancer treatment and regenerative medicine.

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References
1.
Miao J, Kyoyama H, Liu L, Chan G, Wang Y, Urisman A . Inhibition of cyclin-dependent kinase 7 down-regulates yes-associated protein expression in mesothelioma cells. J Cell Mol Med. 2019; 24(1):1087-1098. PMC: 6933402. DOI: 10.1111/jcmm.14841. View

2.
Zhao B, Wei X, Li W, Udan R, Yang Q, Kim J . Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007; 21(21):2747-61. PMC: 2045129. DOI: 10.1101/gad.1602907. View

3.
Harvey K, Pfleger C, Hariharan I . The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003; 114(4):457-67. DOI: 10.1016/s0092-8674(03)00557-9. View

4.
Diamantopoulou Z, White G, Fadlullah M, Dreger M, Pickering K, Maltas J . TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells. Cancer Cell. 2017; 31(5):621-634.e6. PMC: 5425402. DOI: 10.1016/j.ccell.2017.03.007. View

5.
Yao F, Zhou Z, Kim J, Hang Q, Xiao Z, Ton B . SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity. Nat Commun. 2018; 9(1):2269. PMC: 5995870. DOI: 10.1038/s41467-018-04620-y. View