Hypoxia-inducible factor-1α mRNA: a new target for destabilization by tristetraprolin in endothelial cells

Chamboredon, Sandrine; Ciais, Delphine; Desroches-Castan, Agnès; Savi, Pierre; Bono, Françoise; Feige, Jean‐Jacques; Cherradi, Nadia

doi:10.1091/mbc.e10-07-0617

Cited by 94 publications

(83 citation statements)

References 51 publications

(67 reference statements)

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“…S4A), which is consistent with the reported differential effects of hypoxia on mRNA levels for HIF-2␣ and HIF-1␣ in HUVEC (Fig. 3D) (29) as well as other cell types (39). Importantly, Dicer overexpression in the setting of hypoxia significantly blunted the luciferase activity of chimeric HIF-2␣ and HIF-1␣ 3Ј-UTR reporters ( Fig.…”

Section: Dicer-dependent Regulation Of Hif-␣ Isoforms and Hypoxiarespsupporting

confidence: 88%

“…Interestingly, Dicer overexpression in chronic hypoxia leads to further decreases in both VEGFR2 protein and especially mRNA. We observed the same effect with HIF-1␣ mRNA (29,39) and luciferase-HIF-1␣-3Ј-UTR construct expression in chronic hypoxia, which are further decreased when Dicer is overexpressed. Thus, we take these data to indicate that even though distinct mRNA species may be differentially up-or down-regulated in hypoxia the loss of Dicer-mediated microRNA repression is nonetheless functionally relevant and important to a broad variety of hypoxiaresponsive genes.…”

Section: Discussionsupporting

confidence: 69%

“…Notably, Dicer overexpression did not affect the hypoxia-mediated changes in mRNA levels of HIF-1␣ or CXCR4 (Fig. 3D) (29,30). Importantly, two recent independent studies that examined the kinetics of microRNA-mediated translational inhibition and mRNA degradation have found that mRNA degradation follows translational inhibition (31,32).…”

Section: Dicer-dependent Regulation Of Hif-␣ Isoforms and Hypoxiarespmentioning

confidence: 82%

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Functional Importance of Dicer Protein in the Adaptive Cellular Response to Hypoxia

Metcalf

Yan

et al. 2012

Journal of Biological Chemistry

134

154

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Background: Functional relationships between the microRNA and cellular hypoxia response pathways are unknown. Results: Dicer is down-regulated in chronic hypoxia; this mechanism maintains the induction of hypoxia-inducible factor-␣ subunits and hypoxia-responsive genes. Conclusion: Loss of Dicer-dependent microRNA regulation is important for maintaining the concerted cellular response to hypoxia. Significance: Altogether, we provide a newer perspective into the post-transcriptional pathways that regulate the cellular hypoxic response.

show abstract

Section: Dicer-dependent Regulation Of Hif-␣ Isoforms and Hypoxiarespsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 69%

Section: Dicer-dependent Regulation Of Hif-␣ Isoforms and Hypoxiarespmentioning

confidence: 82%

See 1 more Smart Citation

Functional Importance of Dicer Protein in the Adaptive Cellular Response to Hypoxia

Metcalf

Yan

et al. 2012

Journal of Biological Chemistry

134

154

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“…In hypoxia, PHD activity is inhibited, leading to increased HIF-1α protein levels (36). However, this mechanism does not sufficiently explain our observation of resolution of HIF-1α expression in prolonged hypoxia, which has also been reported by others (17,37). miRNA-mediated regulation has become a new theory illustrating the resolution of HIF-1α (16).…”

Section: Mir-210 Alleviated Hypoxia-induced Cell Injury and Apoptosismentioning

confidence: 59%

“…HIF-1α is controlled by a series of complex and elaborate mechanisms because of its abovementioned vital function. Several studies have reported an interesting resolution pattern of HIF-1α, which showed that HIF-1α is not continuous, but undergoes a transient increase followed by a decline under hypoxic conditions (16,17). But canonical oxygen-dependent protein degradation mediated by prolyl hydroxylase domain-containing enzymes (PHDs) cannot competently explain this phenomenon (18).…”

mentioning

confidence: 99%

miR-210 Protects Renal Cell Against Hypoxia-induced Apoptosis by Targeting HIF-1 Alpha

Liu

Li²,

He³

et al. 2017

Mol Med

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The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1-α (HIF-1α) activation. ) is known to be induced by HIF-1α and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1α expression by targeting the 3′ untranslated region of HIF-1α mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1α pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1α directly and suppressing HIF-1α pathway activation in vitro.

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PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis

et al. 2018

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Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability and plays important roles in cancer. The mechanisms by which TTP is regulated in breast cancer are poorly understood. Using multiple biochemical approaches, we found that proviral insertion in murine lymphomas 2 (PIM2) is a novel binding partner of TTP. Interestingly, PIM2 decreased TTP protein levels independent of its kinase activity. PIM2 instead targeted TTP protein for degradation via the ubiquitin‐proteasome pathway. Furthermore, immunohistochemical staining showed that PIM2 and TTP protein levels were negatively correlated in human breast cancer samples. Indeed, PIM2 overexpression de‐repressed TTP‐mediated inhibition of breast cancer cell proliferation and migration in vitro and promoted breast tumor xenograft growth in vivo. These findings demonstrate an important role for the PIM2‐TTP complex in breast cancer tumorigenesis, suggesting that PIM2 may represent a potential therapeutic target for breast cancer treatment.

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Hypoxia-inducible factor-1α mRNA: a new target for destabilization by tristetraprolin in endothelial cells

Abstract: The study provides new evidence that the mRNA-destabilizing protein Tristetraprolin is a modulator of HIF-1α mRNA turnover and may contribute to the control of HIF-1α and HIF-1α target gene expression during the adaptive response of endothelial cells to hypoxia.

Cited by 94 publications

References 51 publications

Functional Importance of Dicer Protein in the Adaptive Cellular Response to Hypoxia

Functional Importance of Dicer Protein in the Adaptive Cellular Response to Hypoxia

miR-210 Protects Renal Cell Against Hypoxia-induced Apoptosis by Targeting HIF-1 Alpha

PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis

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