Structural dissection of Hippo signaling

Shi, Zhubing; Shi, Jianzhong; Zhou, Zhaocai

doi:10.1093/abbs/gmu107

Cited by 13 publications

(4 citation statements)

References 119 publications

(167 reference statements)

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“…Among the kinase components of STRIPAK complex, MST1/2 are best known as upstream kinases of the mammalian Hippo signaling pathway 28,29 . In this pathway, MST1/2 activate downstream kinases LATS1/2, together with SAV1 and MOB1A/B.…”

Section: Introductionmentioning

confidence: 99%

Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling

et al. 2019

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Striatin-interacting phosphatases and kinases (STRIPAKs) are evolutionarily conserved supramolecular complexes, which have been implicated in the Hippo signaling pathway. Yet the topological structure and dynamic assembly of STRIPAK complexes remain elusive. Here, we report the overall architecture and substructures of a Hippo kinase-containing STRIPAK complex. PP2Aa/c-bound STRN3 directly contacts the Hippo kinase MST2 and also controls the loading of MST2 via two “arms” in a phosphorylation-dependent manner, one arm being STRIP1 and the other SIKE1-SLMAP. A decreased cell density triggered the dissociation of the STRIP1 arm from STRIPAK, reflecting the dynamic assembly of the complex upon sensing upstream signals. Crystallographic studies defined at atomic resolution the interface between STRN3 and SIKE1, and that between SIKE1 and SLMAP. Disrupting the complex assembly abrogated the regulatory effect of STRIPAK towards Hippo signaling. Collectively, our study revealed a “two-arm” assembly of STRIPAK with context-dependent dynamics, offering a framework for further studies on Hippo signaling and biological processes involving MST kinases.

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Section: Introductionmentioning

confidence: 99%

Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling

et al. 2019

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“…The Hippo signaling pathway is one of the pathways that can play an important role in the survival of cancer cells, with control of proliferation and apoptosis (Yu et al, 2015;Azad et al, 2019). Some important tumor suppressor genes (LATS1 and LATS2) and an oncogene (YAP) exist in this pathway (Shi et al, 2015). Deregulation of the Hippo signaling pathway has a significant effect on growth of some cancers (Yu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Effects of Quinacrine on Expression of Hippo signaling Pathway Components (LATS1, LATS2, and YAP) in Human Breast Cancer Stem Cells

Darbankhales

Mirfakhraie

Ghahremani

et al. 2020

Asian Pac J Cancer Prev

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Objective: The Hippo signaling pathway has important role in the pathogenesis of some tumors. Breast cancer is the most prevalent cancer among females in the world. In recent years, various articles referred to inhibiting effect of quinacrine, a derivative of 9-aminoacridine, on the growth of several types of cancer cells. In this study, we evaluated the effect of quinacrine on expression of LATS1, LATS2, and YAP genes of the Hippo signaling pathway and YAP level in human breast cancer stem cells (MDA-MB 231 cell line). This cell line of breast cancer expresses the triple negative characteristics. Methods: MDA-MB 231 cells was treated with 0.5 µM of quinacrine for 3 days. The dose was selected using MTT assays. The expression of genes was quantified by Real-time PCR. The protein expression was performed by Western blotting. Significance of observations were checked by means of Mann-Whitney test using p<0.05 as the level of significance. Results: The present study demonstrated that expression of YAP gene in MDA-MB 231 cell line significantly down regulated by quinacrine. Quinacrine significantly decreased the amount of YAP protein. Moreover, quinacrine did not have meaningful effect on LATS1 and LATS2 genes expression. Conclusion: YAP gene is an oncogene and inhibition of its expression by quinacrine could effect on breast cancer cell progression.

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“…MST1 and MST2 are major components of the mammalian Hippo signaling pathway, which controls cell number, organ size and tissue homeostasis 345678. Together with SAV1 and MOB1A/B, MST1/2 can activate downstream kinases LATS1/2, leading to the phosphorylation and inhibition of the transcriptional coactivators YAP and TAZ.…”

Section: Introductionmentioning

confidence: 99%

MST kinases in innate immune signaling

Shi¹,

Zhou²

2018

CST

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The mammalian STE20-like (MST) protein kinases are composed of MST1, MST2, MST3, MST4 and YSK1. They play crucial roles in cell growth, migration, polarity and apoptosis. Dysfunction of these kinases often leads to diseases. MST kinases are extensively involved in development and function of immune system. Here, we review recent progresses on the regulatory function of MST kinases in innate immune signaling.

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Structural dissection of Hippo signaling

Cited by 13 publications

References 119 publications

Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling

Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling

Effects of Quinacrine on Expression of Hippo signaling Pathway Components (LATS1, LATS2, and YAP) in Human Breast Cancer Stem Cells

MST kinases in innate immune signaling

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