scholarly journals WW Domain-Containing Proteins YAP and TAZ in the Hippo Pathway as Key Regulators in Stemness Maintenance, Tissue Homeostasis, and Tumorigenesis

2019 ◽  
Vol 9 ◽  
Author(s):  
Yu-An Chen ◽  
Chen-Yu Lu ◽  
Tian-You Cheng ◽  
Szu-Hua Pan ◽  
Hsin-Fu Chen ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Ww Domain ◽  
The Hippo Pathway

scholarly journals Viruses go modular

2020 ◽  
Vol 295 (14) ◽  
pp. 4604-4616 ◽  
Author(s):  
Ariel Shepley-McTaggart ◽  
Hao Fan ◽  
Marius Sudol ◽  
Ronald N. Harty
Keyword(s):  
Hippo Pathway ◽  
Host Proteins ◽  
Dna Viruses ◽  
Ww Domain ◽  
Ww Domains ◽  
Host Interactions ◽  
New Class ◽  
Domain Interactions ◽  
Molecular Aspects ◽  
The Hippo Pathway

The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics.

scholarly journals The Hippo Pathway: Immunity and Cancer

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 94 ◽  
Author(s):  
Zaid Taha ◽  
Helena Janse van Rensburg ◽  
Xiaolong Yang
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mammalian Cells ◽  
Immune Cell ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Hippo Signaling ◽  
Core Components ◽  
The Hippo Pathway ◽  
Future Work

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

scholarly journals Elucidation of WW domain ligand binding specificities in the Hippo pathway reveals STXBP 4 as YAP inhibitor

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Rebecca E Vargas ◽  
Vy Thuy Duong ◽  
Han Han ◽  
Albert Paul Ta ◽  
Yuxuan Chen ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Hippo Pathway ◽  
Ww Domain ◽  
The Hippo Pathway

The Sterile 20-Like Kinase Tao Controls Tissue Homeostasis by Regulating the Hippo Pathway in Drosophila Adult Midgut

2014 ◽  
Vol 41 (8) ◽  
pp. 429-438 ◽  
Author(s):  
Xudong Huang ◽  
Lai Shi ◽  
Jun Cao ◽  
Fangfei He ◽  
Renling Li ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
The Hippo Pathway

scholarly journals Mutations and Copy Number Abnormalities of Hippo Pathway Components in Human Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhengjin He ◽  
Ruihan Li ◽  
Hai Jiang
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Copy Number ◽  
Human Cancer ◽  
Hippo Pathway ◽  
Copy Number Variations ◽  
Tissue Homeostasis ◽  
Hippo Signaling ◽  
Core Components ◽  
The Hippo Pathway

The Hippo pathway is highly conserved from Drosophila to mammals. As a key regulator of cell proliferation, the Hippo pathway controls tissue homeostasis and has a major impact on tumorigenesis. The originally defined core components of the Hippo pathway in mammals include STK3/4, LATS1/2, YAP1/TAZ, TEAD, VGLL4, and NF2. However, for most of these genes, mutations and copy number variations are relatively uncommon in human cancer. Several other recently identified upstream and downstream regulators of Hippo signaling, including FAT1, SHANK2, Gq/11, and SWI/SNF complex, are more commonly dysregulated in human cancer at the genomic level. This review will discuss major genomic events in human cancer that enable cancer cells to escape the tumor-suppressive effects of Hippo signaling.

scholarly journals The role of translationally controlled tumor protein in proliferation ofDrosophilaintestinal stem cells

2019 ◽  
Vol 116 (52) ◽  
pp. 26591-26598 ◽  
Author(s):  
Young V. Kwon ◽  
Bingqing Zhao ◽  
Chiwei Xu ◽  
Jiae Lee ◽  
Chiao-Lin Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Translationally Controlled Tumor Protein ◽  
Cellular Processes ◽  
The Hippo Pathway

Translationally controlled tumor protein (TCTP) is a highly conserved protein functioning in multiple cellular processes, ranging from growth to immune responses. To explore the role of TCTP in tissue maintenance and regeneration, we employed the adultDrosophilamidgut, where multiple signaling pathways interact to precisely regulate stem cell division for tissue homeostasis. Tctp levels were significantly increased in stem cells and enteroblasts upon tissue damage or activation of the Hippo pathway that promotes regeneration of intestinal epithelium. Stem cells with reduced Tctp levels failed to proliferate during normal tissue homeostasis and regeneration. Mechanistically, Tctp forms a complex with multiple proteins involved in translation and genetically interacts with ribosomal subunits. In addition, Tctp increases both Akt1 protein abundance and phosphorylation in vivo. Altogether, Tctp regulates stem cell proliferation by interacting with key growth regulatory signaling pathways and the translation process in vivo.

scholarly journals Citron kinase interacts with LATS2 and inhibits its activity by occluding its hydrophobic phosphorylation motif

2019 ◽  
Vol 11 (11) ◽  
pp. 1006-1017
Author(s):  
Thi Hai Yen Tran ◽  
Dae-Wook Yang ◽  
Minchul Kim ◽  
Da-Hye Lee ◽  
Marta Gai ◽  
...  
Keyword(s):  
Hippo Pathway ◽  
Inhibitory Effect ◽  
Tissue Homeostasis ◽  
Genetic Interactions ◽  
Large Tumor ◽  
Phosphorylation Motif ◽  
Potential Binding ◽  
Citron Kinase ◽  
The Hippo Pathway ◽  
Molecular Crosstalk

Abstract The inhibitory effect of large tumor suppressor kinase (LATS1/2) on the activity of the oncoprotein yes-associated protein (YAP) is crucial to maintain tissue homeostasis. Proteomic studies have identified several new regulators of this process. Recently, citron kinase (CIT) was listed as a potential binding candidate of Hippo-related components, suggesting a new connection between CIT and the Hippo pathway. Aside from CIT’s role in cytokinesis, the molecular crosstalk between CIT and the Hippo pathway is largely unknown. Here, we demonstrate a role for CIT as a scaffold protein linking LATS2 and YAP. More importantly, CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif—targeted by MST1, leading to LATS2 inactivation and YAP activation. By studying their genetic interactions, we found that Sticky, the CIT homolog in Drosophila melanogaster, functions with Warts to control Drosophila eye development. Together, our study confirms citron kinase as a novel regulator of the Hippo pathway.

scholarly journals STK25 suppresses Hippo signaling by regulating SAV1-STRIPAK antagonism

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sung Jun Bae ◽  
Lisheng Ni ◽  
Xuelian Luo
Keyword(s):  
Hippo Pathway ◽  
Human Cells ◽  
Tissue Homeostasis ◽  
Organ Size ◽  
Scaffolding Protein ◽  
Hippo Signaling ◽  
Mutual Antagonism ◽  
Kinase Cascade ◽  
The Hippo Pathway

The MST-LATS kinase cascade is central to the Hippo pathway that controls tissue homeostasis, development, and organ size. The PP2A complex STRIPAKSLMAP blocks MST1/2 activation. The GCKIII family kinases associate with STRIPAK, but the functions of these phosphatase-associated kinases remain elusive. We previously showed that the scaffolding protein SAV1 promotes Hippo signaling by counteracting STRIPAK (Bae et al., 2017). Here, we show that the GCKIII kinase STK25 promotes STRIPAK-mediated inhibition of MST2 in human cells. Depletion of STK25 enhances MST2 activation without affecting the integrity of STRIPAKSLMAP. STK25 directly phosphorylates SAV1 and diminishes the ability of SAV1 to inhibit STRIPAK. Thus, STK25 as the kinase component of STRIPAK can inhibit the function of the STRIPAK inhibitor SAV1. This mutual antagonism between STRIPAK and SAV1 controls the initiation of Hippo signaling.

scholarly journals Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Xue Hao ◽  
Shimin Wang ◽  
Yi Lu ◽  
Wentao Yu ◽  
Pengyue Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Intestinal Stem Cell ◽  
Hippo Signaling ◽  
Intestinal Function ◽  
Independent Manner ◽  
The Hippo Pathway ◽  
Basal Proliferation

Tissue homeostasis and regeneration in the Drosophila midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation by sequestering the transcription co-factor Yorkie (Yki) in the cytoplasm, a factor required for rapid ISC proliferation under injury-induced regeneration. Nonetheless, the mechanism of Hippo-mediated midgut homeostasis and whether canonical Hippo signaling is involved in ISC basal proliferation are less characterized. Here we identify Lola as a transcription factor acting downstream of Hippo signaling to restrict ISC proliferation in a Yki-independent manner. Not only that Lola interacts with and is stabilized by the Hippo signaling core kinase Warts (Wts), Lola rescues the enhanced ISC proliferation upon Wts depletion via suppressing Dref and SkpA expressions. Our findings reveal that Lola is a non-canonical Hippo signaling component in regulating midgut homeostasis, providing insights on the mechanism of tissue maintenance and intestinal function.

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