Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase.

Abstract:

:Although cells express hundreds of metalloenzymes, the mechanisms by which apoenzymes receive their metal cofactors are largely unknown. Poly(rC)-binding proteins PCBP1 and PCBP2 are multifunctional adaptor proteins that bind iron and deliver it to ferritin for storage or to prolyl and asparagyl hydroxylases to metallate the mononuclear iron center. Here, we show that PCBP1 and PCBP2 also deliver iron to deoxyhypusine hydroxylase (DOHH), the dinuclear iron enzyme required for hypusine modification of the translation factor eukaryotic initiation factor 5A. Cells depleted of PCBP1 or PCBP2 exhibited loss of DOHH activity and loss of the holo form of the enzyme in cells, particularly when cells were made mildly iron-deficient. Lysates containing PCBP1 and PCBP2 converted apo-DOHH to holo-DOHH in vitro with greater efficiency than lysates lacking PCBP1 or PCBP2. PCBP1 bound to DOHH in iron-treated cells but not in control or iron-deficient cells. Depletion of PCBP1 or PCBP2 had no effect on the cytosolic Fe-S cluster enzyme xanthine oxidase but led to loss of cytosolic aconitase activity. Loss of aconitase activity was not accompanied by gain of RNA-binding activity, a pattern suggesting the incomplete disassembly of the [4Fe-4S] cluster. PCBP depletions had minimal effects on total cellular iron, mitochondrial iron levels, and heme synthesis. Thus, PCBP1 and PCBP2 may serve as iron chaperones to multiple classes of cytosolic nonheme iron enzymes and may have a particular role in restoring metal cofactors that are spontaneously lost in iron deficient cells.

authors

Frey AG,Nandal A,Park JH,Smith PM,Yabe T,Ryu MS,Ghosh MC,Lee J,Rouault TA,Park MH,Philpott CC

doi

10.1073/pnas.1402732111

subject

Has Abstract

pub_date

2014-06-03 00:00:00

pages

8031-6

issue

22

eissn

0027-8424

issn

1091-6490

pii

1402732111

journal_volume

111

pub_type

杂志文章
  • Costs, needs, and integration efforts shape helping behavior toward refugees.

    abstract::Recent political instabilities and conflicts around the world have drastically increased the number of people seeking refuge. The challenges associated with the large number of arriving refugees have revealed a deep divide among the citizens of host countries: one group welcomes refugees, whereas another rejects them....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1805601115

    authors: Böhm R,Theelen MMP,Rusch H,Van Lange PAM

    更新日期:2018-07-10 00:00:00

  • A sulfated carbohydrate epitope inhibits axon regeneration after injury.

    abstract::Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but the structural diversity of their polysaccharides has hampered efforts to dissect the structure-activity relationships underlying their physiological activity. By taking advantage of our a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1121318109

    authors: Brown JM,Xia J,Zhuang B,Cho KS,Rogers CJ,Gama CI,Rawat M,Tully SE,Uetani N,Mason DE,Tremblay ML,Peters EC,Habuchi O,Chen DF,Hsieh-Wilson LC

    更新日期:2012-03-27 00:00:00

  • Reciprocal effects of an inhibitory factor on catalytic activity and noncatalytic cGMP binding sites of rod phosphodiesterase.

    abstract::In illuminated rod outer segment membranes, GTP and guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) have reciprocal effects on cGMP phosphodiesterase (PDEase; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) activity and cGMP binding to noncatalytic sites on that enzyme. Two micromolar p[NH]ppG inc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.12.3702

    authors: Yamazaki A,Bartucca F,Ting A,Bitensky MW

    更新日期:1982-06-01 00:00:00

  • Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles.

    abstract::Membraneless organelles contain a wide spectrum of molecular chaperones, indicating their important roles in modulating the metastable conformation and biological function of membraneless organelles. Here we report that class I and II Hsp40 (DNAJ) proteins possess a high ability of phase separation rendered by the fle...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2002437117

    authors: Gu J,Liu Z,Zhang S,Li Y,Xia W,Wang C,Xiang H,Liu Z,Tan L,Fang Y,Liu C,Li D

    更新日期:2020-12-08 00:00:00

  • Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor.

    abstract::The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF rece...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.12.5082

    authors: Kitamura T,Hayashida K,Sakamaki K,Yokota T,Arai K,Miyajima A

    更新日期:1991-06-15 00:00:00

  • Economic and geographic drivers of wildlife consumption in rural Africa.

    abstract::The harvest of wildlife for human consumption is valued at several billion dollars annually and provides an essential source of meat for hundreds of millions of rural people living in poverty. This harvest is also considered among the greatest threats to biodiversity throughout Africa, Asia, and Latin America. Economi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1011526108

    authors: Brashares JS,Golden CD,Weinbaum KZ,Barrett CB,Okello GV

    更新日期:2011-08-23 00:00:00

  • Poly(A) binding protein abundance regulates eukaryotic translation initiation factor 4F assembly in human cytomegalovirus-infected cells.

    abstract::By commandeering cellular translation initiation factors, or destroying those dispensable for viral mRNA translation, viruses often suppress host protein synthesis. In contrast, cellular protein synthesis proceeds in human cytomegalovirus (HCMV)-infected cells, forcing viral and cellular mRNAs to compete for limiting ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1202829109

    authors: McKinney C,Perez C,Mohr I

    更新日期:2012-04-10 00:00:00

  • Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics.

    abstract::Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210096109

    authors: Marrache S,Dhar S

    更新日期:2012-10-02 00:00:00

  • Pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis.

    abstract::Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wild-type BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1119949109

    authors: De Semir D,Nosrati M,Bezrookove V,Dar AA,Federman S,Bienvenu G,Venna S,Rangel J,Climent J,Meyer Tamgüney TM,Thummala S,Tong S,Leong SP,Haqq C,Billings P,Miller JR 3rd,Sagebiel RW,Debs R,Kashani-Sabet M

    更新日期:2012-05-01 00:00:00

  • Oscillatory singular integrals and harmonic analysis on nilpotent groups.

    abstract::Several related classes of operators on nilpotent Lie groups are considered. These operators involve the following features: (i) oscillatory factors that are exponentials of imaginary polynomials, (ii) convolutions with singular kernels supported on lower-dimensional submanifolds, (iii) validity in the general context...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.1.1

    authors: Ricci F,Stein EM

    更新日期:1986-01-01 00:00:00

  • Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles.

    abstract::Proteases constitute the largest enzyme family, yet their biological roles are obscured by our rudimentary understanding of their cellular substrates. There are 12 human caspases that play crucial roles in inflammation and cell differentiation and drive the terminal stages of cell death. Recent N-terminomics technolog...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1524900113

    authors: Julien O,Zhuang M,Wiita AP,O'Donoghue AJ,Knudsen GM,Craik CS,Wells JA

    更新日期:2016-04-05 00:00:00

  • Parallel zippers formed by alpha-helical peptide columns in crystals of Boc-Aib-Glu(OBzl)-Leu-Aib-Ala-Leu-Aib-Ala-Lys(Z)-Aib-OMe.

    abstract::The crystal structure of the decapeptide Boc-Aib-Glu(OBzl)-Leu-Aib-Ala-Leu-Aib-Ala-Lys(Z)-Aib-OMe (where Aib is alpha-aminoisobutyryl, Boc is t-butoxycarbonyl, OBzl is benzyl ester, and Z is benzyloxycarbonyl) illustrates a parallel zipper arrangement of interacting helical peptide columns. Head-to-tail NH...OC hydrog...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.20.7921

    authors: Karle IL,Flippen-Anderson JL,Uma K,Balaram P

    更新日期:1990-10-01 00:00:00

  • Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption.

    abstract::The mechanisms by which phosphorus homeostasis is preserved in mammals are not completely understood. We demonstrate the presence of a mechanism by which the intestine detects the presence of increased dietary phosphate and rapidly increases renal phosphate excretion. The mechanism is of physiological relevance becaus...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0704446104

    authors: Berndt T,Thomas LF,Craig TA,Sommer S,Li X,Bergstralh EJ,Kumar R

    更新日期:2007-06-26 00:00:00

  • An α/β-hydrolase fold protein in the biosynthesis of thiostrepton exhibits a dual activity for endopeptidyl hydrolysis and epoxide ring opening/macrocyclization.

    abstract::Thiostrepton (TSR), an archetypal bimacrocyclic thiopeptide antibiotic that arises from complex posttranslational modifications of a genetically encoded precursor peptide, possesses a quinaldic acid (QA) moiety within the side-ring system of a thiopeptide-characteristic framework. Focusing on selective engineering of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1612607113

    authors: Zheng Q,Wang S,Duan P,Liao R,Chen D,Liu W

    更新日期:2016-12-13 00:00:00

  • Self/nonself recognition in ascidian fertilization: vitelline coat protein HrVC70 is a candidate allorecognition molecule.

    abstract::Ascidians are hermaphrodites releasing sperm and eggs simultaneously, but many species are self-sterile because of a self/nonself-recognition system in spermegg interaction. Here, we show that a 70-kDa vitelline coat protein, HrVC70, consisting of 12 epidermal growth factor-like repeats, plays a key role in self/nonse...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0401928101

    authors: Sawada H,Tanaka E,Ban S,Yamasaki C,Fujino J,Ooura K,Abe Y,Matsumoto K,Yokosawa H

    更新日期:2004-11-02 00:00:00

  • Human cytomegalovirus latent infection of granulocyte-macrophage progenitors.

    abstract::We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulocyte-macrophage progenitors, a suspected natural site of viral latency, and have established conditions for latent infection and reactivation in this cell population. Progenitor cells from human fetal liver or bone marrow ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.25.11879

    authors: Kondo K,Kaneshima H,Mocarski ES

    更新日期:1994-12-06 00:00:00

  • Isolation and characterization of a cDNA clone for the complete protein coding region of the delta subunit of the mouse acetylcholine receptor.

    abstract::A mouse cDNA clone has been isolated that contains the complete coding region of a protein highly homologous to the delta subunit of the Torpedo acetylcholine receptor (AcChoR). The cDNA library was constructed in the vector lambda 10 from membrane-associated poly(A)+ RNA from BC3H-1 mouse cells. Surprisingly, the del...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.24.7970

    authors: LaPolla RJ,Mayne KM,Davidson N

    更新日期:1984-12-01 00:00:00

  • Nuclear magnetic resonance imaging and spectroscopy of human brain function.

    abstract::The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.90.8.3127

    authors: Shulman RG,Blamire AM,Rothman DL,McCarthy G

    更新日期:1993-04-15 00:00:00

  • Temporal regulation in development: negative and positive cis regulators dictate the precise timing of expression of a Drosophila chorion gene.

    abstract::We have used germ-line transformation to dissect the cis regulatory elements responsible for the transcriptional control of an internally marked Drosophila chorion gene (s15-P) during development. A 73-base-pair segment of the proximal 5'-flanking DNA contains sequences essential for the tissue-specific expression and...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.9.3029

    authors: Mariani BD,Lingappa JR,Kafatos FC

    更新日期:1988-05-01 00:00:00

  • Local demographic changes and US presidential voting, 2012 to 2016.

    abstract::Immigration and demographic change have become highly salient in American politics, partly because of the 2016 campaign of Donald Trump. Previous research indicates that local influxes of immigrants or unfamiliar ethnic groups can generate threatened responses, but has either focused on nonelectoral outcomes or analyz...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1909202116

    authors: Hill SJ,Hopkins DJ,Huber GA

    更新日期:2019-12-10 00:00:00

  • SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling.

    abstract::Engagement of the T cell antigen receptor (TCR) leads to rapid activation of protein tyrosine kinases, which in turn phosphorylate downstream enzymes and adapter proteins. Some adapter proteins, such as SLP-76, Vav, and LAT, positively regulate TCR-mediated signal transduction, whereas others, such as Cbl, play an inh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.17.9775

    authors: Tang J,Sawasdikosol S,Chang JH,Burakoff SJ

    更新日期:1999-08-17 00:00:00

  • Local adaptation in Trinidadian guppies alters ecosystem processes.

    abstract::Theory suggests evolutionary change can significantly influence and act in tandem with ecological forces via ecological-evolutionary feedbacks. This theory assumes that significant evolutionary change occurs over ecologically relevant timescales and that phenotypes have differential effects on the environment. Here we...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0908023107

    authors: Bassar RD,Marshall MC,López-Sepulcre A,Zandonà E,Auer SK,Travis J,Pringle CM,Flecker AS,Thomas SA,Fraser DF,Reznick DN

    更新日期:2010-02-23 00:00:00

  • Inhibition and stimulation of the development of the bioluminescent system in Beneckea harveyi by cyclic GMP.

    abstract::The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These ob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.12.4454

    authors: Ulitzur S,Yashphe J,Hastings JW

    更新日期:1976-12-01 00:00:00

  • Direct isolation of human BRCA2 gene by transformation-associated recombination in yeast.

    abstract::Mutant forms of the BRCA2 gene contribute significantly to hereditary breast cancer. Isolation of the normal and mutant forms of the BRCA2 gene with its natural promoter would greatly facilitate analysis of the gene and its contribution to breast cancer. We have accomplished the direct isolation of the 90-kb gene from...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.14.7384

    authors: Larionov V,Kouprina N,Solomon G,Barrett JC,Resnick MA

    更新日期:1997-07-08 00:00:00

  • Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle.

    abstract::Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1117885109

    authors: Jang E,Albadawi H,Watkins MT,Edelman ER,Baker AB

    更新日期:2012-01-31 00:00:00

  • Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool.

    abstract::Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that contribute little to synchronous release during action potentials but are release competent when stimulated by sucrose or by direct intracellular application of calcium. It has been noted that the proximity of a release-competent SV to the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114072109

    authors: Lee JS,Ho WK,Lee SH

    更新日期:2012-03-27 00:00:00

  • PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer.

    abstract::PIK3CA mutations are reported to be present in approximately 25% of breast cancer (BC), particularly the estrogen receptor-positive (ER+) and HER2-overexpressing (HER2+) subtypes, making them one of the most common genetic aberrations in BC. In experimental models, these mutations have been shown to activate AKT and i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907011107

    authors: Loi S,Haibe-Kains B,Majjaj S,Lallemand F,Durbecq V,Larsimont D,Gonzalez-Angulo AM,Pusztai L,Symmans WF,Bardelli A,Ellis P,Tutt AN,Gillett CE,Hennessy BT,Mills GB,Phillips WA,Piccart MJ,Speed TP,McArthur GA,Sotiriou

    更新日期:2010-06-01 00:00:00

  • Tumor detection and elimination by a targeted gallium corrole.

    abstract::Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epider...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0901531106

    authors: Agadjanian H,Ma J,Rentsendorj A,Valluripalli V,Hwang JY,Mahammed A,Farkas DL,Gray HB,Gross Z,Medina-Kauwe LK

    更新日期:2009-04-14 00:00:00

  • Independent, specialized invasions of ectomycorrhizal mutualism by two nonphotosynthetic orchids.

    abstract::We have investigated the mycorrhizal associations of two nonphotosynthetic orchids from distant tribes within the Orchidaceae. The two orchids were found to associate exclusively with two distinct clades of ectomycorrhizal basidiomycetous fungi over wide geographic ranges. Yet both orchids retained the internal mycorr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.9.4510

    authors: Taylor DL,Bruns TD

    更新日期:1997-04-29 00:00:00

  • Bromodomain 4 activation predicts breast cancer survival.

    abstract::Previous work identified the Rap1 GTPase-activating protein Sipa1 as a germ-line-encoded metastasis modifier. The bromodomain protein Brd4 physically interacts with and modulates the enzymatic activity of Sipa1. In vitro analysis of a highly metastatic mouse mammary tumor cell line ectopically expressing Brd4 demonstr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710331105

    authors: Crawford NP,Alsarraj J,Lukes L,Walker RC,Officewala JS,Yang HH,Lee MP,Ozato K,Hunter KW

    更新日期:2008-04-29 00:00:00