High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling

Globus, Oriane; Evron, Tamar; Caspi, Michal; Siman-Tov, Ronen; Rosin‐Arbesfeld, Rina

doi:10.1038/s41598-017-18203-2

Cited by 25 publications

(29 citation statements)

References 46 publications

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“…An XTT proliferation assay was used to evaluate the impact of the best peptide inhibitors of BTLA/HVEM complex formation on the proliferation of peripheral blood mononuclear cells. This assay is widely utilized in the measurement of a broad spectrum of biologically active compounds, in order to assess their impact on cell proliferation and, thus, indirectly, cell cytotoxicity [38,39]. The effect of gD(1-38)(L4C-R36C), gD(1-38)(L4C-V37C), and gD(1-36)(K10C-T29C) on cell proliferation, and indirectly cell cytotoxicity, was examined in PBMCs from healthy volunteers.…”

Section: Xtt Cell Proliferation Assaymentioning

confidence: 99%

Fragments of gD Protein as Inhibitors of BTLA/HVEM Complex Formation - Design, Synthesis, and Cellular Studies

Kuncewicz

Battin

Sieradzan

et al. 2020

IJMS

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One of the major current trends in cancer immunotherapy is the blockade of immune checkpoint proteins that negatively regulate the immune response. This has been achieved through antibodies blocking PD-1/PD-L1 and CTLA-4/CD80/CD86 interactions. Such antibodies have revolutionized oncological therapy and shown a new way to fight cancer. Additional (negative) immune checkpoints are also promising targets in cancer therapy and there is a demand for inhibitors for these molecules. Our studies are focused on BTLA/HVEM complex, which inhibits T-cell proliferation and cytokine production and therefore has great potential as a new target for cancer treatment. The goal of the presented studies was the design and synthesis of compounds able to block BTLA/HVEM interactions. For that purpose, the N-terminal fragment of glycoprotein D (gD), which interacts with HVEM, was used. Based on the crystal structure of the gD/HVEM complex and MM/GBSA analysis performed on it, several peptides were designed and synthesized as potential inhibitors of the BTLA/HVEM interaction. Affinity tests, ELISA tests, and cellular-based reporter assays were performed on these compounds to check their ability to bind to HVEM and to inhibit BTLA/HVEM complex formation. For leading peptides candidates, all-atom and subsequent docking simulations with a coarse-grained force field were performed to determine their binding modes. To further evaluate their potential as drug candidates, their stability in plasma and their cytotoxicity effects on PBMCs were assessed. Our data indicate that the peptide gD(1-36)(K10C-T29C) is the best candidate as a future drug. It interacts with HVEM protein, blocks the BTLA/HVEM interaction, and is nontoxic to cells. The present study provides a new perspective on the development of BTLA/HVEM inhibitors that disrupt protein interactions.

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Section: Xtt Cell Proliferation Assaymentioning

confidence: 99%

Fragments of gD Protein as Inhibitors of BTLA/HVEM Complex Formation - Design, Synthesis, and Cellular Studies

Kuncewicz

Battin

Sieradzan

et al. 2020

IJMS

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“…Interestingly, a recent study demonstrated thrombospondin-1 is a substrate for HtrA1, and proteolytically released fragment of thrombospondin-1 promotes tube formation by endothelial cells [91]. Moreover, independent of catalytic activity, secreted HtrA1 inhibits transforming growth factor (TGF)-β/BMP signaling pathways by interacting with their receptors and inhibit Wnt pathway by interacting with β-catenin [92].…”

Section: Degradation Of Divergent Ecm Proteinsmentioning

confidence: 99%

Asian age-related macular degeneration: from basic science research perspective

Yanagi

Foo

Yoshida

2018

Eye

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In Asian populations, polypoidal choroidal vasculopathy (PCV), a distinct phenotype of neovascular age-related macular degeneration (AMD), is more prevalent than Caucasians. Recently, there has been significant focus on how PCV differs from typical AMD. Although typical AMD and PCV share a variety of mechanisms by which abnormal angiogenic process occurs at the retinochoroidal interface, PCV has different clinical characteristics such as aneurysm-like dilation at the terminal of choroidal neovascular membranes, less frequent drusen and inner choroidal degeneration due to the thickened choroid. Recent studies support an important role for inflammation, angiogenesis molecules and lipid metabolism in the pathogenesis of neovascular AMD. Furthermore, although less attention has been paid to the role of the choroid in AMD, accumulating evidence suggests that the choriocapillaris and choroid also play a pivotal role in drusenogenesis, typical AMD and PCV. This review discusses the basic pathogenic mechanisms of AMD and explores the difference between typical AMD and PCV.

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“…It has been documented that abnormal constitutive of several signaling pathways are implicated in tumorigenesis of CRC, especial Wnt/β‐catenin signaling (Globus et al, ). The Wnt/β‐catenin signaling is classified into canonical and non‐canonical pathways.…”

Section: Introductionmentioning

confidence: 99%

MNX1 promotes cell proliferation and activates Wnt/β‐catenin signaling in colorectal cancer

Yang¹,

Pan²,

et al. 2019

Cell Biology International

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Aberrant Wnt/b-catenin signaling is a characteristic feature of colorectal cancer (CRC), therefore, understanding the underlying mechanisms of aberrant Wnt/b-catenin signaling will improve the treatment outcome of CRC. Expression of MNX1 in paired fresh CRC tissues and corresponding adjacent normal tissues were examined by qPCR and Western blotting. The levels of MNX1 in paraffin-embedded CRC specimens were detected by immunohistochemistry (IHC). The role of MNX1 in growth and proliferation of CRC cells was evaluated by MTT and colony formation assay. Luciferase reporter analysis and western blotting were carried out to explore the influence of MNX1 on Wnt/b-catenin signaling. The results showed that expression of MNX1 is markedly upregulated in CRC tissues and positively correlated with level of Ki67, and overexpression of MNX1 significantly promotes the proliferation of CRC cells. Further study showed that ectopic expression of MNX1 activates the Wnt/b-catenin signaling and upregulates the expression of c-Myc and CCND1, the downstream genes of Wnt/b-catenin signaling. Therefore, MNX1 plays an indispensable role in promoting of human CRC progression and may represent a novel therapeutic target for CRC.

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High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling

Cited by 25 publications

References 46 publications

Fragments of gD Protein as Inhibitors of BTLA/HVEM Complex Formation - Design, Synthesis, and Cellular Studies

Fragments of gD Protein as Inhibitors of BTLA/HVEM Complex Formation - Design, Synthesis, and Cellular Studies

Asian age-related macular degeneration: from basic science research perspective

MNX1 promotes cell proliferation and activates Wnt/β‐catenin signaling in colorectal cancer

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