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Article ; Online: Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis

Yinan Yang / Huijing Zhou / Xiawei Huang / Chengfang Wu / Kewei Zheng / Jingrong Deng / Yonggang Zheng / Jiahui Wang / Xiaofeng Chi / Xianjue Ma / Huimin Pan / Rui Shen / Duojia Pan / Bo Liu

Nature Communications, Vol 15, Iss 1, Pp 1-

2024 Volume 17

Abstract: Abstract The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is ... ...

Abstract	Abstract The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Receptor-Mediated Endocytosis of Nanoparticles: Roles of Shapes, Orientations, and Rotations of Nanoparticles

Tang, Huayuan / Hongfei Ye / Hongwu Zhang / Yonggang Zheng

Journal of physical chemistry. 2018 Jan. 11, v. 122, no. 1

2018

Abstract: A complete understanding of the interactions between nanoparticles (NPs) and the cell membrane is essential for the potential biomedical applications of NPs. The rotation of the NP during the cellular wrapping process is of great biological significance ... ...

Abstract	A complete understanding of the interactions between nanoparticles (NPs) and the cell membrane is essential for the potential biomedical applications of NPs. The rotation of the NP during the cellular wrapping process is of great biological significance and has been widely observed in experiments and simulations. However, the underlying mechanisms of the rotation and their potential influences on the wrapping behavior are far from being fully understood. Here, by coupling the rotation of the NP with the diffusion of the receptors, we set up a model to theoretically investigate the wrapping pathway and the internalization rate of the rotatable NP in the receptor-mediated endocytosis. Based on this model, it is found that the endocytosis proceeds through the symmetric–asymmetric or asymmetric–symmetric–asymmetric wrapping pathway due to the bending and membrane tension competition induced rotation of NP. In addition, we show that the wrapping rate in the direction that the wrapping proceeds can be largely accelerated by the rotation. Moreover, the time to fully wrap the NP depends not only on the size and shape of the NP but also on its rotation and initial orientation. These results reveal the roles of the shape, rotation, and initial orientation of the NP on the receptor-mediated endocytosis and may provide guidelines for the design of NP-based drug delivery systems.
Keywords	cell membranes ; drug delivery systems ; endocytosis ; guidelines ; models ; nanoparticles ; physical chemistry ; receptors
Language	English
Dates of publication	2018-0111
Size	p. 171-180.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5207
DOI	10.1021/acs.jpcb.7b09619
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An adjustable permeation membrane up to the separation for multicomponent gas mixture

Hongfei Ye / Dong Li / Xin Ye / Yonggang Zheng / Zhongqiang Zhang / Hongwu Zhang / Zhen Chen

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 8

Abstract: Abstract The mixture separation is of fundamental importance in the modern industry. The membrane-based separation technology has attracted considerable attention due to the high efficiency, low energy consumption, etc. However, the tradeoff between the ... ...

Abstract	Abstract The mixture separation is of fundamental importance in the modern industry. The membrane-based separation technology has attracted considerable attention due to the high efficiency, low energy consumption, etc. However, the tradeoff between the permeability and selectivity is a crucial challenge, which is also difficult to adjust during the separation process. Based on the salt water-filled carbon nanotubes, a separation membrane with the adjustable molecular channels by the electric field is proposed in this work. The separation mechanism is clarified on the basis of the characteristic size of the molecular channel and the overall effective diameter of gas molecules. The molecular dynamics simulation is performed to examine the feasibility and validity of the designed separation membrane. The simulations on the binary gas mixture (H2 and N2) reveal the flow control and high-purity separation as the electric field intensity varies. As for the mixed gas with the three components (H2, N2 and Xe), the successive separations and the switch between the high-efficiency and high-purity separation could be achieved only through adjusting the electric field intensity. This work incorporates the control into the membrane-based separation technology, which provides a novel solution for the complex industrial separation requirement.
Keywords	Medicine ; R ; Science ; Q
Subject code	600
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Radial stability and configuration transition of carbon nanotubes regulated by enclosed cores

Yonggang Zheng / Haitang He / Hongfei Ye

AIP Advances, Vol 5, Iss 5, Pp 057155-057155-

2015 Volume 7

Abstract: The radial stability and configuration transition of carbon nanotubes (CNTs) with enclosed cores have been studied in this paper by using atomistic simulations. We found that an abnormal transition of CNTs from open to collapse can be regulated by ... ...

Abstract	The radial stability and configuration transition of carbon nanotubes (CNTs) with enclosed cores have been studied in this paper by using atomistic simulations. We found that an abnormal transition of CNTs from open to collapse can be regulated by enclosing deformable and rigid cores. The energy barrier for the configuration transition can be reduced by nearly one order of magnitude due to the presence of these cores, i.e., from ∼0.3 eV/Å to ∼0.03 eV/Å. These findings may provide guidance for the design of controllable CNT-based carrier systems for the delivery of drug, gene and fluid.
Keywords	Science ; Q ; Science (General) ; Q1-390 ; Physics ; QC1-999
Language	English
Publishing date	2015-05-01T00:00:00Z
Publisher	AIP Publishing LLC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nerfin-1 represses transcriptional output of Hippo signaling in cell competition

Pengfei Guo / Chang-Hyun Lee / Huiyan Lei / Yonggang Zheng / Katiuska Daniela Pulgar Prieto / Duojia Pan

eLife, Vol

2019 Volume 8

Abstract: The Hippo tumor suppressor pathway regulates tissue growth in Drosophila by restricting the activity of the transcriptional coactivator Yorkie (Yki), which normally complexes with the TEF/TEAD family DNA-binding transcription factor Scalloped (Sd) to ... ...

Abstract	The Hippo tumor suppressor pathway regulates tissue growth in Drosophila by restricting the activity of the transcriptional coactivator Yorkie (Yki), which normally complexes with the TEF/TEAD family DNA-binding transcription factor Scalloped (Sd) to drive the expression of growth-promoting genes. Given its pivotal role as a central hub in mediating the transcriptional output of Hippo signaling, there is great interest in understanding the molecular regulation of the Sd-Yki complex. In this study, we identify Nerfin-1 as a transcriptional repressor that antagonizes the activity of the Sd-Yki complex by binding to the TEA DNA-binding domain of Sd. Consistent with its biochemical function, ectopic expression of Nerfin-1 results in tissue undergrowth in an Sd-dependent manner. Conversely, loss of Nerfin-1 enhances the ability of winner cells to eliminate loser cells in multiple scenarios of cell competition. We further show that INSM1, the mammalian ortholog of Nerfin-1, plays a conserved role in repressing the activity of the TEAD-YAP complex. These findings reveal a novel regulatory mode converging on the transcriptional output of the Hippo pathway that may be exploited for modulating the YAP oncoprotein in cancer and regenerative medicine.
Keywords	Hippo signaling ; cell competition ; transcription factors ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Homeostatic Control of Hpo/MST Kinase Activity through Autophosphorylation-Dependent Recruitment of the STRIPAK PP2A Phosphatase Complex

Yonggang Zheng / Bo Liu / Li Wang / Huiyan Lei / Katiuska Daniela Pulgar Prieto / Duojia Pan

Cell Reports, Vol 21, Iss 12, Pp 3612-

2017 Volume 3623

Abstract: Summary: The Hippo pathway controls organ size and tissue homeostasis through a kinase cascade leading from the Ste20-like kinase Hpo (MST1/2 in mammals) to the transcriptional coactivator Yki (YAP/TAZ in mammals). Whereas previous studies have uncovered ...

Abstract	Summary: The Hippo pathway controls organ size and tissue homeostasis through a kinase cascade leading from the Ste20-like kinase Hpo (MST1/2 in mammals) to the transcriptional coactivator Yki (YAP/TAZ in mammals). Whereas previous studies have uncovered positive and negative regulators of Hpo/MST, how they are integrated to maintain signaling homeostasis remains poorly understood. Here, we identify a self-restricting mechanism whereby autophosphorylation of an unstructured linker in Hpo/MST creates docking sites for the STRIPAK PP2A phosphatase complex to inactivate Hpo/MST. Mutation of the phospho-dependent docking sites in Hpo/MST or deletion of Slmap, the STRIPAK subunit recognizing these docking sites, results in constitutive activation of Hpo/MST in both Drosophila and mammalian cells. In contrast, autophosphorylation of the Hpo/MST linker at distinct sites is known to recruit Mats/MOB1 to facilitate Hippo signaling. Thus, multisite autophosphorylation of Hpo/MST linker provides an evolutionarily conserved built-in molecular platform to maintain signaling homeostasis by coupling antagonistic signaling activities. : The Hippo pathway was named after the Ste20-like kinase Hpo/MST, but how its activity is regulated remains unclear. Zheng et al. identify a self-restricting mechanism whereby autophosphorylation of an unstructured linker in Hpo/MST creates docking sites for the STRIPAK PP2A phosphatase complex to inactivate Hpo/MST in both Drosophila and mammals. Keywords: Hippo signaling, Hpo, MST1/2, STRIPAK, PP2A, SLMAP, autophosphorylation
Keywords	Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2017-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila

Liu, Bo / Yonggang Zheng / Feng Yin / Jianzhong Yu / Neal Silverman / Duojia Pan

Cell. 2016 Jan. 28, v. 164

2016

Abstract: The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innateÂ immunity ... ...

Abstract	The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innateÂ immunity whereby Yorkie directly regulates the transcription of the Drosophila IÎºB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactusÂ mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection byÂ Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IÎºB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings.
Keywords	Drosophila ; Gram-positive bacteria ; antimicrobial peptides ; cacti and succulents ; fat body ; homeostasis ; innate immunity ; messenger RNA ; phosphorylation ; signal transduction
Language	English
Dates of publication	2016-0128
Size	p. 406-419.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2015.12.029
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Spectrin regulates Hippo signaling by modulating cortical actomyosin activity

Hua Deng / Wei Wang / Jianzhong Yu / Yonggang Zheng / Yun Qing / Duojia Pan

eLife, Vol

2015 Volume 4

Abstract: The Hippo pathway controls tissue growth through a core kinase cascade that impinges on the transcription of growth-regulatory genes. Understanding how this pathway is regulated in development remains a major challenge. Recent studies suggested that ... ...

Abstract	The Hippo pathway controls tissue growth through a core kinase cascade that impinges on the transcription of growth-regulatory genes. Understanding how this pathway is regulated in development remains a major challenge. Recent studies suggested that Hippo signaling can be modulated by cytoskeletal tension through a Rok-myosin II pathway. How cytoskeletal tension is regulated or its relationship to the other known upstream regulators of the Hippo pathway remains poorly defined. In this study, we identify spectrin, a contractile protein at the cytoskeleton-membrane interface, as an upstream regulator of the Hippo signaling pathway. We show that, in contrast to canonical upstream regulators such as Crumbs, Kibra, Expanded, and Merlin, spectrin regulates Hippo signaling in a distinct way by modulating cortical actomyosin activity through non-muscle myosin II. These results uncover an essential mediator of Hippo signaling by cytoskeleton tension, providing a new entry point to dissecting how mechanical signals regulate Hippo signaling in living tissues.
Keywords	organ size ; signal transduction ; cytoskeleton ; myosin activity ; cell tension ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2015-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Premetazoan Origin of the Hippo Signaling Pathway

Arnau Sebé-Pedrós / Yonggang Zheng / Iñaki Ruiz-Trillo / Duojia Pan

Cell Reports, Vol 1, Iss 1, Pp 13-

2012 Volume 20

Abstract: Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of ...

Abstract	Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Hippo effector Yorkie activates transcription by interacting with a histone methyltransferase complex through Ncoa6

Yun Qing / Feng Yin / Wei Wang / Yonggang Zheng / Pengfei Guo / Frederick Schozer / Hua Deng / Duojia Pan

eLife, Vol

2014 Volume 3

Abstract: The Hippo signaling pathway regulates tissue growth in Drosophila through the transcriptional coactivator Yorkie (Yki). How Yki activates target gene transcription is poorly understood. Here, we identify Nuclear receptor coactivator 6 (Ncoa6), a subunit ... ...

Abstract	The Hippo signaling pathway regulates tissue growth in Drosophila through the transcriptional coactivator Yorkie (Yki). How Yki activates target gene transcription is poorly understood. Here, we identify Nuclear receptor coactivator 6 (Ncoa6), a subunit of the Trithorax-related (Trr) histone H3 lysine 4 (H3K4) methyltransferase complex, as a Yki-binding protein. Like Yki, Ncoa6 and Trr are functionally required for Hippo-mediated growth control and target gene expression. Strikingly, artificial tethering of Ncoa6 to Sd is sufficient to promote tissue growth and Yki target expression even in the absence of Yki, underscoring the importance of Yki-mediated recruitment of Ncoa6 in transcriptional activation. Consistent with the established role for the Trr complex in histone methylation, we show that Yki, Ncoa6, and Trr are required for normal H3K4 methylation at Hippo target genes. These findings shed light on Yki-mediated transcriptional regulation and uncover a potential link between chromatin modification and tissue growth.
Keywords	Hippo signaling ; transcription factor ; growth control ; histone methylation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2014-07-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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