PERK/eIF2α signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1α translation

Ivanova, Iglika G.; Park, Catherine V.; Yemm, Adrian I.; Kenneth, Niall S.

doi:10.1093/nar/gky127

Cited by 47 publications

(47 citation statements)

References 42 publications

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“…The YB-1 involvement in translation or stability depends on cellular conditions. For example, with simultaneous unfolded protein response (UPR) and hypoxia, YB-1 fails to stimulate HIF-1α mRNA translation [152]. The authors explain this fact by a decreased YB-1 ability to bind the 5 UTR of HIF-1α mRNA [152].…”

Section: Modulating Activity Of Yb Proteins In Translation and Stabilitymentioning

confidence: 99%

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

et al. 2020

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Y-box binding proteins (YB proteins) are DNA/RNA-binding proteins belonging to a large family of proteins with the cold shock domain. Functionally, these proteins are known to be the most diverse, although the literature hardly offers any molecular mechanisms governing their activities in the cell, tissue, or the whole organism. This review describes the involvement of YB proteins in RNA-dependent processes, such as mRNA packaging into mRNPs, mRNA translation, and mRNA stabilization. In addition, recent data on the structural peculiarities of YB proteins underlying their interactions with nucleic acids are discussed.

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Section: Modulating Activity Of Yb Proteins In Translation and Stabilitymentioning

confidence: 99%

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

et al. 2020

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“…Tests conducted in three different cell lines (cervical and prostate cancer as well as fibrosarcoma) led to the hypothesis that tumor-caused hypoxia most likely induces PKC isoform-dependent HIF-1a accumulations. Cell line studies have shown that the HIF1alpha activation was initiated by the AKT-mTOR and NF-kB cascade [90,91].…”

Section: Hypoxic Modulation Of Carcinogenesis Via Mtor Signalingmentioning

confidence: 99%

The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

Sobočan

Bračič

Knez

et al. 2020

Cancers

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Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. It has been shown that women with increased levels of mTOR signaling pathway targets have worse prognosis compared to women with normal mTOR levels. Yet, targeting mTOR alone has led to unsatisfactory outcomes in gynecological cancer. The aim of our review was therefore to provide an overview of the most recent clinical results and basic findings on the interplay of mTOR signaling and cold shock proteins in gynecological malignancies. Due to their oncogenic activity, there are promising data showing that mTOR and Y-box-protein 1 (YB-1) dual targeting improves the inhibition of carcinogenic activity. Although several components differentially expressed in patients with ovarian, endometrial, and cervical cancer of the mTOR were identified, there are only a few investigated downstream actors in gynecological cancer connecting them with YB-1. Our analysis shows that YB-1 is an important player impacting AKT as well as the downstream actors interacting with mTOR such as epidermal growth factor receptor (EGFR), Snail or E-cadherin.

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“…These enzymes are not designed to be in the cytoplasm, and we reason that this release could result in various stress signals leading to inhibition of HIF-1a accumulation. In addition, late endosomes and lysosomes are targets for misfolded protein degradation, and the release of increased amounts of misfolded proteins may result in PERK activation which has previously been shown to result in HIF-1a inhibition (Ivanova et al, 2018;Jackson and Hewitt, 2016).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HIF-1α accumulation in prostate cancer cells is initiated during early stages of mammalian orthoreovirus infection

Bussiere

Miller

2020

Preprint

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Mammalian orthoreovirus (MRV) is a safe and effective cancer killing virus that has completed Phase I-III clinical trials against numerous cancer types. While many patients experience benefit from MRV therapy, pre-defined set points necessary for FDA approval have not been reached. Therefore, additional research into MRV biology and the effect of viral therapy on different tumor genetic subtypes and microenvironments is necessary to identify tumors most amenable to MRV virotherapy. In this work we analyzed the stage of viral infection necessary to inhibit HIF-1α, an aggressive cancer activator induced by hypoxia. We ruled out a number of viral proteins and the virus genome as being necessary and determined that a step parallel with virus core movement across the endosomal membrane was required for this inhibition. Altogether, this work clarifies the mechanisms of MRV-induced HIF-1α inhibition and provides biological relevance for using MRV to inhibit the devastating effects of tumor hypoxia.

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PERK/eIF2α signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1α translation

Cited by 47 publications

References 42 publications

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

Inhibition of HIF-1α accumulation in prostate cancer cells is initiated during early stages of mammalian orthoreovirus infection

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