WeightNameValue
1000 Titel
  • Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2
1000 Autor/in
  1. Giménez-Mascarell, Paula |
  2. Oyenarte, Iker |
  3. Hardy, Serge |
  4. Breiderhoff, Tilman |
  5. Stuiver, Marchel |
  6. Kostantin, Elie |
  7. Diercks, Tammo |
  8. Pey, Angel L. |
  9. Ereño-Orbea, June |
  10. Martínez-Chantar, María Luz |
  11. Khalaf-Nazzal, Reham |
  12. Claverie-Martin, Felix |
  13. Müller, Dominik |
  14. Tremblay, Michel L. |
  15. Alfonso Martínez-Cruz, Luis |
1000 Erscheinungsjahr 2016
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-11-29
1000 Erschienen in
1000 Quellenangabe
  • 292(3): 786-801
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247653/ |
  • http://dx.doi.org/10.1074/jbc.M116.759944 |
1000 Ergänzendes Material
  • http://www.jbc.org/cgi/content/full/M116.759944/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Phosphatases of regenerating liver (PRLs), the most oncogenic of all protein-tyrosine phosphatases (PTPs), play a critical role in metastatic progression of cancers. Recent findings established a new paradigm by uncovering that their association with magnesium transporters of the cyclin M (CNNM) family causes a rise in intracellular magnesium levels that promote oncogenic transformation. Recently, however, essential roles for regulation of the circadian rhythm and reproduction of the CNNM family have been highlighted. Here, we describe the crystal structure of PRL-1 in complex with the Bateman module of CNNM2 (CNNM2BAT), which consists of two cystathionine β-synthase (CBS) domains (IPR000664) and represents an intracellular regulatory module of the transporter. The structure reveals a heterotetrameric association, consisting of a disc-like homodimer of CNNM2BAT bound to two independent PRL-1 molecules, each one located at opposite tips of the disc. The structure highlights the key role played by Asp-558 at the extended loop of the CBS2 motif of CNNM2 in maintaining the association between the two proteins and proves that the interaction between CNNM2 and PRL-1 occurs via the catalytic domain of the phosphatase. Our data shed new light on the structural basis underlying the interaction between PRL phosphatases and CNNM transporters and provides a hypothesis about the molecular mechanism by which PRL-1, upon binding to CNNM2, might increase the intracellular concentration of Mg2+ thereby contributing to tumor progression and metastasis. The availability of this structure sets the basis for the rational design of compounds modulating PRL-1 and CNNM2 activities.
1000 Sacherschließung
lokal cell proliferation
lokal PRL-1, CNNM2, CBS domain
lokal transporter
lokal magnesium
lokal cancer
lokal phosphatase
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/R2ltw6luZXotTWFzY2FyZWxsLCBQYXVsYQ==|https://frl.publisso.de/adhoc/creator/T3llbmFydGUsIElrZXI=|https://frl.publisso.de/adhoc/creator/SGFyZHksIFNlcmdl|https://frl.publisso.de/adhoc/creator/QnJlaWRlcmhvZmYsIFRpbG1hbg==|https://frl.publisso.de/adhoc/creator/U3R1aXZlciwgTWFyY2hlbA==|https://frl.publisso.de/adhoc/creator/S29zdGFudGluLCBFbGll|https://frl.publisso.de/adhoc/creator/RGllcmNrcywgVGFtbW8=|https://frl.publisso.de/adhoc/creator/UGV5LCBBbmdlbCBMLg==|https://frl.publisso.de/adhoc/creator/RXJlw7FvLU9yYmVhLCBKdW5l|https://frl.publisso.de/adhoc/creator/TWFydMOtbmV6LUNoYW50YXIsIE1hcsOtYSBMdXo=|https://frl.publisso.de/adhoc/creator/S2hhbGFmLU5henphbCwgUmVoYW0=|https://frl.publisso.de/adhoc/creator/Q2xhdmVyaWUtTWFydGluLCBGZWxpeA==|https://frl.publisso.de/adhoc/creator/TcO8bGxlciwgRG9taW5paw==|https://frl.publisso.de/adhoc/creator/VHJlbWJsYXksIE1pY2hlbCBMLg==|https://frl.publisso.de/adhoc/creator/QWxmb25zbyBNYXJ0w61uZXotQ3J1eiwgTHVpcw==
1000 Förderer
  1. Departamento de Educacion, Universidades e Investigacion del Gobierno Vasco |
  2. Departamento de Industria, Innovacion, Comercio y Turismo del Gobierno Vasco |
  3. Diputacion Foral de Bizkaia |
  4. Spanish Ministerio de Ciencia e Innovacion (MICINN) |
  5. Spanish Ministry of Economy and Competitiveness |
  6. Ministerio de Ciencia e Innovacion CONSOLIDER-INGENIO |
1000 Fördernummer
  1. PI2010-17
  2. ETORTEK IE05-14; IE07-202
  3. 7/13/08/2006/11; 7/13/08/2005/14
  4. BFU2010-17857
  5. CSD2008-00005
  6. BFU2013-47531-R
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
  5. -
  6. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Departamento de Educacion, Universidades e Investigacion del Gobierno Vasco |
    1000 Förderprogramm -
    1000 Fördernummer PI2010-17
  2. 1000 joinedFunding-child
    1000 Förderer Departamento de Industria, Innovacion, Comercio y Turismo del Gobierno Vasco |
    1000 Förderprogramm -
    1000 Fördernummer ETORTEK IE05-14; IE07-202
  3. 1000 joinedFunding-child
    1000 Förderer Diputacion Foral de Bizkaia |
    1000 Förderprogramm -
    1000 Fördernummer 7/13/08/2006/11; 7/13/08/2005/14
  4. 1000 joinedFunding-child
    1000 Förderer Spanish Ministerio de Ciencia e Innovacion (MICINN) |
    1000 Förderprogramm -
    1000 Fördernummer BFU2010-17857
  5. 1000 joinedFunding-child
    1000 Förderer Spanish Ministry of Economy and Competitiveness |
    1000 Förderprogramm -
    1000 Fördernummer CSD2008-00005
  6. 1000 joinedFunding-child
    1000 Förderer Ministerio de Ciencia e Innovacion CONSOLIDER-INGENIO |
    1000 Förderprogramm -
    1000 Fördernummer BFU2013-47531-R
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6402274.rdf
1000 Erstellt am 2017-05-04T13:55:11.024+0200
1000 Erstellt von 25
1000 beschreibt frl:6402274
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Wed Jun 20 13:00:50 CEST 2018
1000 Objekt bearb. Wed Jun 20 13:00:50 CEST 2018
1000 Vgl. frl:6402274
1000 Oai Id
  1. oai:frl.publisso.de:frl:6402274 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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