Regulation of Hypoxia-Inducible Factor 1<i>α</i> during Hypoxia by DAP5-Induced Translation of PHD2

Bryant, Jeffrey D.; Brown, Michael C.; Dobrikov, Mikhail I.; Dobrikova, Elena Y.; Gemberling, Sarah; Zhang, Qing; Gromeier, Matthias

doi:10.1128/mcb.00647-17

Cited by 18 publications

(22 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The assay was conducted 3 times with similar outcomes; results from a representative test are depicted. distinct from those for eIF4G1/2, that hinge on inducible DAP5:eIF2␤ binding (18). eIF4G2 is homologous to eIF4G1 with identical binding partners; however, it is expressed at an ϳ1:10 ratio (19) and lacks key posttranslational IDL modifications, e.g., a PKC␣ site at S1186 or the adjacent S1188 (10) and an ERK1/2/CDK1 site at S1232 (6,9).…”

Section: Resultsmentioning

confidence: 99%

Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation

Dobrikov

Dobrikova

Gromeier

2018

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Eukaryotic ribosomes contain the high-affinity protein kinase C βII (PKCβII) scaffold, receptor for activated C kinase (RACK1), but its role in protein synthesis control remains unclear. We found that RACK1:PKCβII phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at S1093 and eIF3a at S1364. We showed that reversible eIF4G(S1093) phosphorylation is involved in a global protein synthesis surge upon PKC-Raf-extracellular signal-regulated kinase 1/2 (ERK1/2) activation and in induction of phorbol ester-responsive transcripts, such as cyclooxygenase 2 (Cox-2) and cyclin-dependent kinase inhibitor (p21), or in 5' 7-methylguanosine (mG) cap-independent enterovirus translation. Comparison of mRNA and protein levels revealed that eIF4G1 or RACK1 depletion blocked phorbol ester-induced Cox-2 or p21 expression mostly at the translational level, whereas PKCβ inhibition reduced them both at the translational and transcript levels. Our findings reveal a physiological role for ribosomal RACK1 in providing the molecular scaffold for PKCβII and its role in coordinating the translational response to PKC-Raf-ERK1/2 activation.

show abstract

Section: Resultsmentioning

confidence: 99%

Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation

Dobrikov

Dobrikova

Gromeier

2018

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hypoxia-inducible factors (HIFs), prolyl hydroxylases (PHDs), factor-inhibiting HIF-1 (FIH-1), activator protein 1 (AP-1), nuclear factor (NF)-κB, p53 and c-Myc are the most well-understood factors that influence oxygen regulation in vivo [Podar and Anderson, 2010]. Out of these, HIFs are typically considered as the body’s ‘master oxygen sensors’ and belong to a family of transcriptional factors with many downstream actions [Bryant et al, 2018]. The mechanisms related to oxygen sensing and homeostasis through HIFs have been discussed in detail elsewhere and can be found in reviews such as: [Ivan et al, 2001; Maltepe and Saugstad, 2009; Araldi and Schipani, 2010; Semenza, 2010; Zimna and Kurpisz, 2015; Deng et al, 2016; Graham and Presnell, 2017].…”

Section: Oxygen In Embryonic Developmentmentioning

confidence: 99%

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

Fathollahipour

Patil

Leipzig³

2018

Cells Tissues Organs

View full text Add to dashboard Cite

Oxygen is a vital source of energy necessary to sustain and complete embryonic development. Not only is oxygen the driving force for many cellular functions and metabolism, but it is also involved in regulating stem cell fate, morphogenesis, and organogenesis. Low oxygen levels are the naturally preferred microenvironment for most processes during early development and mainly drive proliferation. Later on, more oxygen and also nutrients are needed for organogenesis and morphogenesis. Therefore, it is critical to maintain oxygen levels within a narrow range as required during development. Modulating oxygen tensions is performed via oxygen homeostasis mainly through the function of hypoxia-inducible factors. Through the function of these factors, oxygen levels are sensed and regulated in different tissues, starting from their embryonic state to adult development. To be able to mimic this process in a tissue engineering setting, it is important to understand the role and levels of oxygen in each developmental stage, from embryonic stem cell differentiation to organogenesis and morphogenesis. Taking lessons from native tissue microenvironments, researchers have explored approaches to control oxygen tensions such as hemoglobin-based, perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic tissue engineering scaffolds and organoids, with the aim of overcoming insufficient or nonuniform oxygen levels and nutrient supply.

show abstract

“…This raises the question as to the identity of translatome remodelers that target different mRNA populations to bring about global, stimuli-induced translatome reprogramming 25,32 , especially in response to physiological stimuli e.g., hypoxia [33][34][35] . Recent work indicates that adaptive translatome remodeling is driven by specialized translation machineries 36,37 , such as the hypoxic cap-binding complex eIF4F H (consisting of eIF4E2 38 and eIF4G3) 25,39 , eIF4E3 40 , eIF3d 37 , DAP5 41,42 , and eIF5B 43 . Yet, general translation factors per se possess only limited capabilities to discriminate between mRNAs.…”

mentioning

confidence: 99%

A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism

Balukoff

Theodoridis

et al. 2020

Nat Commun

View full text Add to dashboard Cite

Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Here, we uncover a network of RNA-binding proteins (RBPs) that enhances the translation efficiency of glycolytic proteins in cells responding to oxygen deprivation. A system-wide proteomic survey of translational engagement identifies a family of oxygen-regulated RBPs that functions as a switch of glycolytic intensity. Tandem mass tagpulse SILAC (TMT-pSILAC) and RNA sequencing reveals that each RBP controls a unique but overlapping portfolio of hypoxic responsive proteins. These RBPs collaborate with the hypoxic protein synthesis apparatus, operating as a translation efficiency checkpoint that integrates upstream mRNA signals to activate anaerobic metabolism. This system allows anoxiaresistant animals and mammalian cells to initiate anaerobic glycolysis and survive hypoxia. We suggest that an oxygen-sensitive RBP cluster controls anaerobic metabolism to confer hypoxia tolerance.

show abstract

Regulation of Hypoxia-Inducible Factor 1α during Hypoxia by DAP5-Induced Translation of PHD2

Cited by 18 publications

References 56 publications

Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation

Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism

Contact Info

Product

Resources

About