The P-body component USP52/PAN2 is a novel regulator of <i>HIF1A</i> mRNA stability

Bett, John S.; Ibrahim, Adel; Garg, Amit K.; Kelly, Van; Pedrioli, Patrick G. A.; Rocha, Sónia; Hay, Ronald T.

doi:10.1042/bj20130026

Cited by 49 publications

(51 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, HIF‐1 is degraded under prolonged hypoxia (Millonig et al ., ). We found that chemical hypoxia decreased HIF‐1α mRNA, in agreement with data previously reported for other cell types (Uchida et al ., ; Bett et al ., ). We also observed that chemical hypoxia induced a rapid stabilization of HIF‐1α protein and a weak increase in HIF‐1α mRNA levels at very early times, after the addition of CoCl 2 .…”

Section: Discussionmentioning

confidence: 99%

The endoplasmic reticulum stress and the HIF‐1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia

López-Hernández

Ceña

Posadas

2015

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEHypoxia inducible factor-1 (HIF-1) promotes transitory neuronal survival suggesting that additional mechanisms such as the endoplasmic reticulum (ER) stress might be involved in determining neuronal survival or death. Here, we examined the involvement of ER stress in hypoxia-induced neuronal death and analysed the relationship between ER stress and the HIF-1 pathways. EXPERIMENTAL APPROACHCultures of rat cortical neurons were exposed to chemical hypoxia induced by 200 μM CoCl2, and its effect on neuronal viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and counting apoptotic nuclei. Protein levels were determined by Western blot analysis. RT-PCR was performed to analyse the content and the t1/2 of HIF-1α mRNA. KEY RESULTSChemical hypoxia induced neuronal apoptosis in a time-dependent manner and activated the ER stress PRK-like endoplasmic reticulum kinase (PERK)-dependent pathway. At later stages, chemical hypoxia increased the expression of the C/EBP homologous protein (CHOP) and caspase 12 activity. CoCl2 reduced HIF-1α mRNA t1/2 leading to a decrease in HIF-1α mRNA and protein content, simultaneously activating the ER stress PERK-dependent pathway. Salubrinal, a selective inhibitor of phospho-eIF2α phosphatase, protected neurons from chemical hypoxia by reducing CHOP levels and caspase 12 activity, and increasing the t1/2 of HIF-1α mRNA and the levels of HIF-1α protein. Knocking down HIF-1α blocked the neuroprotective effects of salubrinal. CONCLUSIONS AND IMPLICATIONSNeuronal apoptosis induced by chemical hypoxia is a process regulated by HIF-1α stabilization early on and by ER stress activation at later stages. Our data also suggested that HIF-1α levels were regulated by ER stress. AbbreviationsATF, activating transcription factor; CHOP, C/EBP homologous protein; ddH2O, double distillate water; DIV, days in vitro; eIF2α, initiation elongation factor 2α; EPO, erythropoietin; ER, endoplasmic reticulum; GLUT1, glucose transporter 1; GRP-78/Bip, glucose-regulated protein 78; HIF-1, hypoxia inducible factor-1; IRE1α, inositol-requiring 1 α; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PERK, PRK-like endoplasmic reticulum kinase; TMRM, tetramethylrhodamine methyl ester BJP British Journal of Pharmacology

show abstract

Section: Discussionmentioning

confidence: 99%

The endoplasmic reticulum stress and the HIF‐1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia

López-Hernández

Ceña

Posadas

2015

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Our findings suggest that ANDV infection may alter hypoxia-directed REDD1 induction, stability, or TSC1/TSC2 regulation, which normally inhibits mTOR activation (45,61,62,69). A suggested role for the hantavirus N protein in altered P-body-directed microRNA responses (65,(93)(94)(95) may contribute to this pathway activation, since microRNA levels altered by hantavirus infection regulate pathways that activate TORC1 and stabilize HIF1␣ (93,94,96). Alternatively, ANDV-altered hypoxic responses could be the result of ANDV effects on a variety of pathways that impact mTOR (31,61,69,89).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Induces Permeability and Giant Cell Responses of Andes Virus-Infected Pulmonary Endothelial Cells by Activating the mTOR-S6K Signaling Pathway

Gavrilovskaya

Gorbunova

Mackow

2013

J Virol

View full text Add to dashboard Cite

show abstract

“…However, Edc3 has an additional structural role in the assembly of cytoplasmic foci of mRNA and proteins involved in mRNA degradation in other contexts (Decker et al, 2007; Teixeira and Parker, 2007). These structures, termed cytoplasmic processing bodies (P bodies), contain the Ccr4/Not and Pan2/3 deadenylase complexes in addition to decapping factors (Bett et al, 2013; Cougot et al, 2004; Teixeira and Parker, 2007). Cytoplasmic mRNA decay is thought to occur within P bodies since they contain decaying mRNA (Sheth and Parker, 2003).…”

Section: Introductionmentioning

confidence: 99%

The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae

et al. 2016

View full text Add to dashboard Cite

The rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC) reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization.

show abstract

The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA stability

Cited by 49 publications

References 40 publications

The endoplasmic reticulum stress and the HIF‐1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia

The endoplasmic reticulum stress and the HIF‐1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia

Hypoxia Induces Permeability and Giant Cell Responses of Andes Virus-Infected Pulmonary Endothelial Cells by Activating the mTOR-S6K Signaling Pathway

The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae

Contact Info

Product

Resources

About