PERK mediates the IRES-dependent translational activation of mRNAs encoding angiogenic growth factors after ischemic stress

Philippe, Céline; Dubrac, Alexandre; Quelen, Cathy; Desquesnes, Aurore; Berghe, L. Van Den; Ségura, Christèle; Filleron, Thomas; Pyronnet, Stéphane; Prats, Hervé; Brousset, Pierre; Touriol, Christian

doi:10.1126/scisignal.aaf2753

Cited by 34 publications

(39 citation statements)

References 41 publications

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“…The role of eIF2 has also been investigated for cellular internal initiation. Importantly, IRES-mediated mRNAs translation can operate upon global protein synthesis attenuation induced by eIF2 phosphorylation [116,[122][123][124][125][126][127]. In addition to the involvement of canonical initiation factors, efficient IRES-dependent translation requires auxiliary RNA-binding proteins, known as IRES trans-acting factors (ITAFs; Figure 2B) [128].…”

Section: Ires-dependent Translation Initiationmentioning

confidence: 99%

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Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers

Jaud

Philippe

Bella

et al. 2020

Cells

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During carcinogenesis, almost all the biological processes are modified in one way or another. Among these biological processes affected, anomalies in protein synthesis are common in cancers. Indeed, cancer cells are subjected to a wide range of stresses, which include physical injuries, hypoxia, nutrient starvation, as well as mitotic, oxidative or genotoxic stresses. All of these stresses will cause the accumulation of unfolded proteins in the Endoplasmic Reticulum (ER), which is a major organelle that is involved in protein synthesis, preservation of cellular homeostasis, and adaptation to unfavourable environment. The accumulation of unfolded proteins in the endoplasmic reticulum causes stress triggering an unfolded protein response in order to promote cell survival or to induce apoptosis in case of chronic stress. Transcription and also translational reprogramming are tightly controlled during the unfolded protein response to ensure selective gene expression. The majority of stresses, including ER stress, induce firstly a decrease in global protein synthesis accompanied by the induction of alternative mechanisms for initiating the translation of mRNA, later followed by a translational recovery. After a presentation of ER stress and the UPR response, we will briefly present the different modes of translation initiation, then address the specific translational regulatory mechanisms acting during reticulum stress in cancers and highlight the importance of translational control by ER stress in tumours.

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Section: Ires-dependent Translation Initiationmentioning

confidence: 99%

“…It was already demonstrated that VEGF-A, FGF-2 and DLL4 IRESs are activated upon stress conditions including hypoxia or ER stress and that these mRNAs remain efficiently translated under ER stress conditions despite phosphorylation of the major PERK substrate, eIF2α [123,124,142,168].…”

Section: The Angiogenesis Paradigmmentioning

confidence: 99%

Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers

Jaud

Philippe

Bella

et al. 2020

Cells

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“…Hence, mRNAs essential for cell survival and for stress response are translated via an IRES‐mediated mechanism . Cellular IRESs thereby allow cells to go through apoptosis, mitosis, or angiogenesis . Additionally, IRESs also aid in the translation of proteins encoded by mRNAs with highly structured 5′ UTRs, where the accessibility of the cap‐binding complex is limited (Fig ).…”

Section: Modes Of Translation Initiationmentioning

confidence: 99%

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

2018

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Recent work has brought to light many different mechanisms of translation initiation that function in cells in parallel to canonical cap-dependent initiation. This has important implications for cancer. Canonical cap-dependent translation initiation is inhibited by many stresses such as hypoxia, nutrient limitation, proteotoxic stress, or genotoxic stress. Since cancer cells are often exposed to these stresses, they rely on alternate modes of translation initiation for protein synthesis and cell growth. Cancer mutations are now being identified in components of the translation machinery and in -regulatory elements of mRNAs, which both control translation of cancer-relevant genes. In this review, we provide an overview on the various modes of non-canonical translation initiation, such as leaky scanning, translation re-initiation, ribosome shunting, IRES-dependent translation, and mA-dependent translation, and then discuss the influence of stress on these different modes of translation. Finally, we present examples of how these modes of translation are dysregulated in cancer cells, allowing them to grow, to proliferate, and to survive, thereby highlighting the importance of translational control in cancer.

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“…In eukaryotes, most translation initiation events rely on binding of the cap-binding complex at the 5' end of mRNA [30,31]. However, under the conditions of impaired canonical cap-dependent translation, cap-independent translation is required for cell survival and stress recovery [32][33][34]. During this process, 40S ribosomes can be directly recruited via an internal ribosome entry site (IRES) element to the 5' untranslated region (UTR) of mRNA [35,36].…”

Section: Bidirectional Translational Reprogrammingmentioning

confidence: 99%

The role of CSDE1 in translational reprogramming and human diseases

2020

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CSDE1 (cold shock domain containing E1) plays a key role in translational reprogramming, which determines the fate of a number of RNAs during biological processes. Interestingly, the role of CSDE1 is bidirectional. It not only promotes and represses the translation of RNAs but also increases and decreases the abundance of RNAs. However, the mechanisms underlying this phenomenon are still unknown. In this review, we propose a "protein-RNA connector" model to explain this bidirectional role and depict its three versions: sequential connection, mutual connection and facilitating connection. As described in this molecular model, CSDE1 binds to RNAs and cooperates with other protein regulators. CSDE1 connects with different RNAs and their regulators for different purposes. The triple complex of CSDE1, a regulator and an RNA reprograms translation in different directions for each transcript. Meanwhile, a number of recent studies have found important roles for CSDE1 in human diseases. This model will help us to understand the role of CSDE1 in translational reprogramming and human diseases.

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PERK mediates the IRES-dependent translational activation of mRNAs encoding angiogenic growth factors after ischemic stress

Cited by 34 publications

References 41 publications

Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers

Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

The role of CSDE1 in translational reprogramming and human diseases

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