Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ

Zuo, Hao; Wong, Yung Hou

doi:10.1186/s12885-015-1802-z

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…Both these pathways are tightly related to cancer progression and apoptosis. In particular, it has been demonstrated that G protein-coupled receptors are involved in BC progression and that Gq signaling promotes cancer cell apoptosis through phospholipase C [ 77 – 79 ]. On the other hand, protein kinase A signaling has been shown to promote mammary tumorigenesis [ 80 ] and to determine ERα repositioning at promoters and tamoxifen resistance [ 81 ]; its inhibition by ERβ–AGO2 cooperation may thus negatively affect cancer cell proliferation and survival.…”

Section: Discussionmentioning

confidence: 99%

The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading

et al. 2017

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BackgroundThe RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease.ResultsApplying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ–AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ − cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability.ConclusionsThese results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1321-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading

et al. 2017

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Reduced Level of Prolylhydroxyproline in the Nail Clippings of Oral Cancer Patients and its Role as an Activator of Phospholipase C-β2

Bhatkar,

Nimburkar,

Raj

et al. 2023

CPPS

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Background: The oral cancer microenvironment plays an important role in the development and progression of the disease which depicts the heterogeneous nature of diseases. Several cellular and non-cellular factors, including dipeptides, have been reported to drive tumor progression and metastasis. Among various secreted molecules in the tumor microenvironment, prolylhydroxyproline (Pro-Hyp) is a collagen-degraded product with specific relevance to fibrosis and oral cancer. However, the detection of Pro-Hyp in the nails of oral cancer patients is a potential biomarker, and our understanding of the biological relevance of Pro-Hyp is highly limited. Methods: Here, the authors have attempted to use a novel and in-house vertical tube gel electrophoresis (VTGE) protocol to evaluate the level of Pro-Hyp in the nails of oral cancer patients and healthy subjects. Furthermore, we employed molecular docking and molecular dynamics (MD) simulations to predict the biological function of Pro-Hyp. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp and a known PLC-β2 activator, m-3M3FBS, were evaluated by the SWISS-ADME server. Results: We report that among various key metabolites, Pro-Hyp, a dipeptide, is reduced in the nails of oral cancer patients. Molecular docking and MD simulations helped to suggest the potential role of Pro-Hyp as an activator of Phospholipase C-β2 (PLC-β2). Pro-Hyp displayed good binding affinity (-7.6 kcal/mol) with specific interactions by a conventional hydrogen bond with key residues, such as HIS311, HIS312, VAL641, and GLU743. MD simulations showed that the activator binding residues and stability of complexes are similar to the well-known activator m-3M3FBS of PLC-β2. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp were found to be highly comparable and even better than those of m-3M3FBS. Conclusion: This study is one of the first reports on Pro-Hyp as a metabolite biomarker in the nails of oral cancer patients. Furthermore, the implications of Pro-Hyp are proposed to activate PLC-β2 as a pro-tumor signaling cascade. In the future, diagnostic and therapeutic approaches may be explored as biomarkers and mimetic of Pro-Hyp.

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Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ

Cited by 2 publications

References 35 publications

The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading

The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading

Reduced Level of Prolylhydroxyproline in the Nail Clippings of Oral Cancer Patients and its Role as an Activator of Phospholipase C-β2

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