EYA1's Conformation Specificity in Dephosphorylating Phosphothreonine in Myc and Its Activity on Myc Stabilization in Breast Cancer.

Abstract:

:EYA1 is known to be overexpressed in human breast cancer, in which the Myc protein is also accumulated in association with decreased phospho-T58 (pT58) levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at pT58 to regulate Myc levels. However, it remains unclear whether EYA1-mediated Myc dephosphorylation on T58 is a critical function in regulating Myc protein stability in breast cancer. Furthermore, EYA1's substrate specificity has remained elusive. In this study, we have investigated these questions, and here, we report that depletion of EYA1 using short hairpin RNA (shRNA) in breast cancer cells destabilizes the Myc protein and increases pT58 levels, leading to an increase in the doubling time and impairment of cell cycle progression. In correlation with EYA1-mediated stabilization of cMyc and reduced levels of pT58, EYA1 greatly reduced cMyc-FBW7 binding and cMyc ubiquitination, thus providing novel insight into how EYA1 acts to regulate the FBW7-mediated Myc degradation machinery. We found that the conserved C-terminal haloacid dehalogenase domain of EYA1, which has been reported to have only tyrosine phosphatase activity, has dual phosphatase activities, and both the N- and C-terminal domains interact with substrates to increase the catalytic activity of EYA1. Enzymatic assay and nuclear magnetic resonance (NMR) analysis demonstrated that EYA1 has a striking conformation preference for phospho-T58 of Myc. Together, our results not only provide novel structural evidence about the conformation specificity of EYA1 in dephosphorylating phosphothreonine in Myc but also reveal an important mechanism contributing to Myc deregulation in human breast cancer.

journal_name

Mol Cell Biol

authors

Li J,Rodriguez Y,Cheng C,Zeng L,Wong EYM,Xu CY,Zhou MM,Xu PX

doi

10.1128/MCB.00499-16

subject

Has Abstract

pub_date

2016-12-19 00:00:00

issue

1

eissn

0270-7306

issn

1098-5549

pii

MCB.00499-16

journal_volume

37

pub_type

杂志文章
  • RAP30/74: a general initiation factor that binds to RNA polymerase II.

    abstract::We have previously shown by affinity chromatography that RAP30 and RAP74 are the mammalian proteins that have the highest affinity for RNA polymerase II. Here we show that RAP30 binds to RAP74 and that the RAP30-RAP74 complex (RAP30/74) is required for accurate initiation by RNA polymerase II. RAP30/74 is required for...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.4.1602

    authors: Burton ZF,Killeen M,Sopta M,Ortolan LG,Greenblatt J

    更新日期:1988-04-01 00:00:00

  • Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb.

    abstract::The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.6.2486-2497.2005

    authors: MacLellan WR,Garcia A,Oh H,Frenkel P,Jordan MC,Roos KP,Schneider MD

    更新日期:2005-03-01 00:00:00

  • Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease.

    abstract::The effect of mammary gland-specific expression of the polyomavirus middle T antigen was examined by establishing lines of transgenic mice that carry the middle T oncogene under the transcriptional control of the mouse mammary tumor virus promoter/enhancer. By contrast to most transgenic strains carrying activated onc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.3.954

    authors: Guy CT,Cardiff RD,Muller WJ

    更新日期:1992-03-01 00:00:00

  • Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase.

    abstract::Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.7.3607

    authors: Belenguer P,Caizergues-Ferrer M,Labbé JC,Dorée M,Amalric F

    更新日期:1990-07-01 00:00:00

  • Isolation of a cDNA clone complementary to sequences for a 34-kilodalton protein which is a pp60v-src substrate.

    abstract::We have isolated a partial cDNA clone containing sequences complementary to a mRNA encoding a 34- to 36-kilodalton normal chicken cell protein which is a substrate for pp60v-src kinase activity. Using this 34-kilodalton cDNA clone as a probe, we determined that the size of the 34-kilodalton mRNA was 1,100 nucleotides ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.9.1935

    authors: Tomasiewicz HG,Cook-Deegan R,Chikaraishi DM

    更新日期:1984-09-01 00:00:00

  • Ribosome stalling is responsible for arginine-specific translational attenuation in Neurospora crassa.

    abstract::The Neurospora crassa arg-2 upstream open reading frame (uORF) plays a role in negative arginine-specific translational regulation. Primer extension inhibition analyses of arg-2 uORF-containing RNA translated in a cell-free system in which arginine-specific regulation was retained revealed "toeprints" corresponding to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.9.4904

    authors: Wang Z,Sachs MS

    更新日期:1997-09-01 00:00:00

  • Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors.

    abstract::Transcriptional activation by nuclear hormone receptors is mediated by the 160-kDa family of nuclear receptor coactivators. These coactivators associate with DNA-bound nuclear receptors and transmit activating signals to the transcription machinery through two activation domains. In screening for mammalian proteins th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.5.1855-1867.2000

    authors: Huang SM,Stallcup MR

    更新日期:2000-03-01 00:00:00

  • The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor beta 1-induced apoptosis of myeloid leukemia cells.

    abstract::Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.4.2352

    authors: Selvakumaran M,Lin HK,Sjin RT,Reed JC,Liebermann DA,Hoffman B

    更新日期:1994-04-01 00:00:00

  • Myocyte enhancer factor 2 activates promoter sequences of the human AbetaH-J-J locus, encoding aspartyl-beta-hydroxylase, junctin, and junctate.

    abstract::Alternative splicing of the locus AbetaH-J-J generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Junctin and junctate are two important proteins...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.8.3261-3275.2005

    authors: Feriotto G,Finotti A,Volpe P,Treves S,Ferrari S,Angelelli C,Zorzato F,Gambari R

    更新日期:2005-04-01 00:00:00

  • Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy.

    abstract::Previous results of our cDNA microarray analysis to look for genes whose expression level correlates well with in vitro tubulogenesis by NP31 endothelial cells revealed the transcription factor ATF3 known to be responsive to stress such as reactive oxygen species (ROS). Anti-ATF3 small interfering RNA gave an inhibito...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.3.1087-1097.2006

    authors: Okamoto A,Iwamoto Y,Maru Y

    更新日期:2006-02-01 00:00:00

  • Selective destabilization of short-lived mRNAs with the granulocyte-macrophage colony-stimulating factor AU-rich 3' noncoding region is mediated by a cotranslational mechanism.

    abstract::The 3' noncoding region element (AUUUA)n specifically targets many short-lived mRNAs for degradation. Although the mechanism by which this sequence functions is not yet understood, a potential link between facilitated mRNA turnover and translation has been implied by the stabilization of cellular mRNAs in the presence...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.3.1971

    authors: Aharon T,Schneider RJ

    更新日期:1993-03-01 00:00:00

  • The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively.

    abstract::In Drosophila melanogaster, X chromosome dosage compensation is achieved by doubling the transcription of most X-linked genes. The male-specific lethal (MSL) complex is required for this process and binds to hundreds of sites on the male X chromosome. The MSL1 protein is essential for X chromosome binding and serves a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.20.8913-8924.2005

    authors: Li F,Parry DA,Scott MJ

    更新日期:2005-10-01 00:00:00

  • Rat metallothionein-1 structural gene and three pseudogenes, one of which contains 5'-regulatory sequences.

    abstract::As shown by Southern blot analysis, the metallothionein-1 (MT-1) genes in rats comprise a multigene family. We present the sequence of the MT-1 structural gene and compare its features with other metallothionein genes. Three MT-1 pseudogenes which we sequenced apparently arose by reverse transcription of processed mRN...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.1.302

    authors: Andersen RD,Birren BW,Taplitz SJ,Herschman HR

    更新日期:1986-01-01 00:00:00

  • Dynamic regulation of histone modifications in Xenopus oocytes through histone exchange.

    abstract::Histone H3 lysine 9 (H3K9) methylation has broad roles in transcriptional repression, gene silencing, maintenance of heterochromatin, and epigenetic inheritance of heterochromatin. Using Xenopus laevis oocytes, we have previously shown that targeting G9a, an H3K9 histone methyltransferase, to chromatin increases H3K9 ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00948-06

    authors: Stewart MD,Sommerville J,Wong J

    更新日期:2006-09-01 00:00:00

  • Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation.

    abstract::Expression of a multidrug resistance gene (mdr1) and its protein product, P-glycoprotein (Pgp), has been correlated with the onset of multidrug resistance in vitro in human cell lines selected for resistance to chemotherapeutic agents derived from natural products. Expression of this gene has also been observed in nor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.10.4337

    authors: Bates SE,Mickley LA,Chen YN,Richert N,Rudick J,Biedler JL,Fojo AT

    更新日期:1989-10-01 00:00:00

  • Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5.

    abstract::Chinese hamster-human interspecific hybrid cells, which contain human chromosome 5 and express four genes linked on that chromosome, were subjected to selective conditions requiring them to retain one of the four linked genes, leuS (encoding leucyl-tRNA synthetase), but lose another, either emtB (encoding ribosomal pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.10.1220

    authors: Dana S,Wasmuth JJ

    更新日期:1982-10-01 00:00:00

  • An upstream open reading frame and the context of the two AUG codons affect the abundance of mitochondrial and nuclear RNase H1.

    abstract::RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in mitochondria results in embryonic lethality due to the failure to amplify mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results from differential translation initiation at two in-frame AUGs (M1 and M27) of a sin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00619-10

    authors: Suzuki Y,Holmes JB,Cerritelli SM,Sakhuja K,Minczuk M,Holt IJ,Crouch RJ

    更新日期:2010-11-01 00:00:00

  • Human colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene.

    abstract::We isolated cDNA clones corresponding to the normal human Ki-ras2 gene and to the transforming allele of the Ki-ras2 gene present in the human colon carcinoma cell line SW480. These two cDNAs encode p21 proteins which differ only at the amino acid at position 12. The normal cDNA encodes a glycine at this position, and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.8.1577

    authors: McCoy MS,Bargmann CI,Weinberg RA

    更新日期:1984-08-01 00:00:00

  • Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes.

    abstract::The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. The farnesoid X receptor (FXR) is a nuclear bile acid receptor controlling bile acid, lipid, and glucose homeostasis. FXR negatively regulates hepatic glyc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01004-12

    authors: Caron S,Huaman Samanez C,Dehondt H,Ploton M,Briand O,Lien F,Dorchies E,Dumont J,Postic C,Cariou B,Lefebvre P,Staels B

    更新日期:2013-06-01 00:00:00

  • The oncogenic forms of N-ras or H-ras prevent skeletal myoblast differentiation.

    abstract::Differentiation of skeletal muscle involves withdrawal of myoblasts from the cell cycle, fusion to form myotubes, and the coordinate expression of a variety of muscle-specific gene products. Fibroblast growth factor and type beta transforming growth factor specifically inhibit myogenesis; however, the transmembrane si...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.6.2104

    authors: Olson EN,Spizz G,Tainsky MA

    更新日期:1987-06-01 00:00:00

  • Involvement of single-stranded tails in homologous recombination of DNA injected into Xenopus laevis oocyte nuclei.

    abstract::Homologous recombination of DNA molecules injected into Xenopus laevis oocyte nuclei is extremely efficient when those molecules are linear and have overlapping homologous ends. It was previously shown that a 5'----3' exonuclease activity in oocytes attacks injected linear DNAs and leaves them with single-stranded 3' ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.6.3268

    authors: Maryon E,Carroll D

    更新日期:1991-06-01 00:00:00

  • Alternative excision products originating from a single integration of polyomavirus DNA.

    abstract::The Cyp cell line consists of mouse cells transformed by a thermosensitive polyomavirus (Py) genome and routinely propagated at 39 degrees C. Cyp cells are readily induced to synthesize free Py DNA by being transferred to 33 degrees C. In one subclone (C12/a1/S48, or S48) of this line, such induction resulted in the i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.10.2608

    authors: Huberdeau D,Sylla BS,Herring-Gillam E,Bourgaux-Ramoisy D,Bourgaux P

    更新日期:1985-10-01 00:00:00

  • The protein level of PGC-1α, a key metabolic regulator, is controlled by NADH-NQO1.

    abstract::PGC-1α is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1α expression is tightly regulated, it is a highly labile protein, and it interacts with various proteins--the known attributes of intrinsically disordered proteins (IDPs). In this study, we characterize PGC-1α as a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01672-12

    authors: Adamovich Y,Shlomai A,Tsvetkov P,Umansky KB,Reuven N,Estall JL,Spiegelman BM,Shaul Y

    更新日期:2013-07-01 00:00:00

  • Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter.

    abstract::Intracisternal A-particle (IAP) expression in mouse cells has been correlated with hypomethylation of HhaI and HpaII sites in proviral long terminal repeats (LTRs). In a previous study, in vitro methylation of three HhaI sites in the U3 region of the LTR from the cloned genomic IAP element, MIA14, was shown to inhibit...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.1.117

    authors: Falzon M,Kuff EL

    更新日期:1991-01-01 00:00:00

  • Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection.

    abstract::Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02253-05

    authors: Bard-Chapeau EA,Yuan J,Droin N,Long S,Zhang EE,Nguyen TV,Feng GS

    更新日期:2006-06-01 00:00:00

  • Plasminogen activator inhibitor type 1 biosynthesis and mRNA level are increased by dexamethasone in human fibrosarcoma cells.

    abstract::Dexamethasone increases type 1 plasminogen activator inhibitor (PAI-1) activity released from the human fibrosarcoma cell line HT-1080. We demonstrated that dexamethasone caused about 10-fold increases in the intracellular and extracellular levels of PAI-1 protein, as measured by an enzyme-linked immunosorbent assay, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.8.3021

    authors: Andreasen PA,Pyke C,Riccio A,Kristensen P,Nielsen LS,Lund LR,Blasi F,Danø K

    更新日期:1987-08-01 00:00:00

  • Effect of undermethylation on mRNA cytoplasmic appearance and half-life.

    abstract::S-Tubercidinylhomocysteine (STH) is a structural analog of S-adenosylhomocysteine and a potent inhibitor of S-adenosylmethionine-dependent methyltransferase reactions. We investigated the effects of STH on HeLa cell mRNA metabolism. Dual labeling studies reveal that STH dramatically inhibits the methylation of HeLa mR...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.3.538

    authors: Camper SA,Albers RJ,Coward JK,Rottman FM

    更新日期:1984-03-01 00:00:00

  • Abortive gap repair: underlying mechanism for Ds element formation.

    abstract::The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous Ds elements is largely unknown. Sequence analysis of native maize Ds elements indicates a complex chimeric structure formed through deletions of Ac sequences with or without insertions of Ac-unrelated sequence blocks. These...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6294

    authors: Rubin E,Levy AA

    更新日期:1997-11-01 00:00:00

  • The product of HUM1, a novel yeast gene, is required for vacuolar Ca2+/H+ exchange and is related to mammalian Na+/Ca2+ exchangers.

    abstract::Calcineurin, or PP2B, plays a critical role in mediating Ca2+-dependent signaling in many cell types. In yeast cells, this highly conserved protein phosphatase regulates aspects of ion homeostasis and cell wall synthesis. We show that calcineurin mutants are sensitive to high concentrations of Mn2+ and identify two ge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.7.3730

    authors: Pozos TC,Sekler I,Cyert MS

    更新日期:1996-07-01 00:00:00

  • Selection of efficient cleavage sites in target RNAs by using a ribozyme expression library.

    abstract::Inactivation of gene expression by antisense mechanisms in general and by ribozymes in particular is a powerful technique for studying the function of a gene product. We have designed a strategy for expression of ribozymes, for selection of accessible cleavage sites in target RNAs, and for isolation of ribozymes from ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.1.540

    authors: Lieber A,Strauss M

    更新日期:1995-01-01 00:00:00