The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway

He, Tian‐Sheng; Dang, Longlong; Zhang, Jiahui; Zhang, Junqi; Wang, Guiping; Wang, Enlin; Xia, Huan; Zhou, Weihong; Wu, Shian; Liu, Xinqi

doi:10.1038/s41418-021-00849-1

Cited by 14 publications

(9 citation statements)

References 72 publications

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“…345 In contrast, LATS2 could support innate immunity by increasing INF-β expression after human immunodeficiency virus-1 infection in vitro, and the loss of LATS2 impaired the innate immune response. 346 Recently, LATS1 was shown to be essential in regulating the activity of type I IFN signalling. 347 Furthermore, the Hippo pathway is important for the function of immune cells that take part in adaptive immunity.…”

Section: Dysregulation Of the Hippo Pathway And Human Diseasesmentioning

confidence: 99%

The Hippo signalling pathway and its implications in human health and diseases

Lan

et al. 2022

Sig Transduct Target Ther

231

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As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in the regulation of numerous biological processes. Thus, substantial efforts have been made to understand the upstream signals that influence the activity of the Hippo pathway, as well as its physiological functions, such as cell proliferation and differentiation, organ growth, embryogenesis, and tissue regeneration/wound healing. However, dysregulation of the Hippo pathway can cause a variety of diseases, including cancer, eye diseases, cardiac diseases, pulmonary diseases, renal diseases, hepatic diseases, and immune dysfunction. Therefore, therapeutic strategies that target dysregulated Hippo components might be promising approaches for the treatment of a wide spectrum of diseases. Here, we review the key components and upstream signals of the Hippo pathway, as well as the critical physiological functions controlled by the Hippo pathway. Additionally, diseases associated with alterations in the Hippo pathway and potential therapies targeting Hippo components will be discussed.

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Section: Dysregulation Of the Hippo Pathway And Human Diseasesmentioning

confidence: 99%

The Hippo signalling pathway and its implications in human health and diseases

Lan

et al. 2022

Sig Transduct Target Ther

231

View full text Add to dashboard Cite

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“…As Upf3b KD in mouse neural progenitor cells leads on the contrary to an increase of cell proliferation (41), additional experiments would be needed to test if UPF3B_S expression increase might participates to the decrease of hNSC proliferation induced by PQBP1 -KD. In addition, several other UPF3B_S-specific interactors are implicated in immune defense against bacterial infection (ex: LTF) while PQBP1 is known to play a role in response to infection as it can recognize viral DNA, interact with cGAS and LATS2 (42) and regulate immune response (16).…”

Section: Discussionmentioning

confidence: 99%

Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome

Courraud

Engel

Quartier

et al. 2022

Preprint

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Mutations in the PQBP1 gene (polyglutamine-binding protein 1) are responsible for a syndromic X-linked form of intellectual disability (XLID), the Renpenning syndrome. PQBP1 encodes a protein that plays a role in the regulation of gene expression, splicing and mRNA translation. To investigate the consequences of variants in PQBP1, we performed transcriptomic studies in 1) patient lymphoblastoid cell lines (LCL) carrying pathogenic variants in PQBP1 and 2) in human neural stem cells (hNSC) knocked-down (KD) for PQBP1. This led to the identification of a hundred dysregulated genes. In particular, we identified an increase in the expression of a non-canonical isoform of another XLID gene, UPF3B. UPF3B plays a crucial role during neurodevelopment by coding for an important actor of the nonsense mRNA mediated decay (NMD) system involved in regulation of protein translation, however, the exact function of the non-canonical isoform, UPF3B_S, is currently unknown. In order to investigate the role of UPF3B_S isoform, we compared the protein interactome of UPF3B_S to the canonical isoform (UPF3B_L). We confirmed that, on the contrary to UPF3B_L, UPF3B_S does not interact with the UPF2/UPF1 complex while it still interacts with exon junction complexes (EJC). However, no notable decrease of NMD pathways was observed in patient LCL or in hNSC KD for PQBP1. We identified several additional protein interactors specific to UPF3B_S. Moreover, we used the increase of UPF3B_S mRNA as a molecular marker to test the pathogenicity of variants of unknown clinical significance identified in individuals with ID in PQPB1. We analyzed patients LCL mRNA as well as blood mRNA samples and performed complementation studies in HeLa cells by overexpressing Wild-type and mutant PQBP1 cDNA. We showed that all these three approaches were efficient to test the effect of variants, at least for variants affecting the CTD domain of the protein. In conclusion, our study provides information on how PQBP1 deficiency may affect the expression of genes and isoforms, such as UPF3B. This informs about the pathological mechanisms involved in Renpenning syndrome but also allows to propose a functional test for variants of unknown significance identified in PQBP1.

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“…Our correlation analysis, enrichment analysis, differential expression analysis and Venn analysis showed that DPEP1 and ASCL2 were signi cantly positively correlated and likely related to the Wnt signaling pathway and Hippo signaling pathway. Recent studies have shown that the Hippo signaling pathway regulates innate immunity in HIV-1 infection or hepatitis B Virus infection and correlates with immune in ltration in lung squamous cell carcinoma [22][23][24]. Furthermore, the Wnt signaling pathway was also associated with immune in ltration in glioblastomas or ovarian cancer [25,26].…”

Section: Discussionmentioning

confidence: 99%

DPEP1 Increases Drug Resistance in an ASCL2-Dependent Manner in Colon Cancer Cells and Correlates with Immune Cell Infiltration

Zeng

Shen

Zhu

et al. 2021

Preprint

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Background: Dipeptidase 1 (DPEP1) is associated with several human cancers. However, its function in colon cancer remains unclear.Methods: DPEP1 expression was analyzed by TCGA and GTEx pancancer data. Survival analysis was performed using the R survival package to assess the prognostic value of the DPEP1 expression level in colon cancer. DPEP1 enrichment analysis was conducted by the clusterProfiler R software package. Correlation analysis, differential expression analysis, and Venn analysis were used to obtain key genes. Correlation of DPEP1 or ASCL2 expression with immune cell infiltration in colon cancer was performed by TIMER and GSCA databases. qRT-PCR, Western blot, Co-immunoprecipitation, dual luciferase reporter experiments, and immunohistochemistry were used to explore the correlation between DPEP1 and ASCL2. MTT was used to evaluate the role of DPEP1 in colon cancer drug resistance.Results: DPEP1 was overexpressed in various cancers, including colon cancer. High DPEP1 expression was negatively correlated with the disease-specific survival (DSS) and progression-free interval (PFI) but not significantly correlated with the overall survival (OS). Enrichment analysis showed that DPEP1 may be related to the Wnt signaling pathway and Hippo signaling pathway. Further analysis showed that DPEP1 and ASCL2 had a strong positive correlation, and both correlated with immune cell infiltration. Moreover, DPEP1 enhanced drug resistance in an ASCL2- dependent manner.Conclusions: Our findings revealed that DPEP1 enhanced drug resistance in an ASCL2-dependent manner and correlated with immune infiltration in colon cancer.

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The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway

Cited by 14 publications

References 72 publications

The Hippo signalling pathway and its implications in human health and diseases

The Hippo signalling pathway and its implications in human health and diseases

Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome

DPEP1 Increases Drug Resistance in an ASCL2-Dependent Manner in Colon Cancer Cells and Correlates with Immune Cell Infiltration

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