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005     20250225092442.0
024 7 _ |a 10.1074/jbc.M116.759944
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024 7 _ |a 1067-8816
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024 7 _ |a 1083-351X
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037 _ _ |a DZNE-2025-00365
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Giménez-Mascarell, Paula
|b 0
245 _ _ |a Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2.
260 _ _ |a Bethesda, MD
|c 2017
|b American Soc. for Biochemistry and Molecular Biology
336 7 _ |a article
|2 DRIVER
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a PRL-1, CNNM2, CBS domain
|2 Other
650 _ 7 |a cancer
|2 Other
650 _ 7 |a cell proliferation
|2 Other
650 _ 7 |a magnesium
|2 Other
650 _ 7 |a phosphatase
|2 Other
650 _ 7 |a transporter
|2 Other
650 _ 7 |a Cation Transport Proteins
|2 NLM Chemicals
650 _ 7 |a Cnnm2 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Immediate-Early Proteins
|2 NLM Chemicals
650 _ 7 |a Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a Protein Tyrosine Phosphatases
|0 EC 3.1.3.48
|2 NLM Chemicals
650 _ 7 |a Ptp4a1 protein, mouse
|0 EC 3.1.3.48
|2 NLM Chemicals
650 _ 7 |a Magnesium
|0 I38ZP9992A
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cation Transport Proteins: chemistry
|2 MeSH
650 _ 2 |a Cation Transport Proteins: genetics
|2 MeSH
650 _ 2 |a Cation Transport Proteins: metabolism
|2 MeSH
650 _ 2 |a Immediate-Early Proteins: chemistry
|2 MeSH
650 _ 2 |a Immediate-Early Proteins: genetics
|2 MeSH
650 _ 2 |a Immediate-Early Proteins: metabolism
|2 MeSH
650 _ 2 |a Magnesium: chemistry
|2 MeSH
650 _ 2 |a Magnesium: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neoplasm Metastasis
|2 MeSH
650 _ 2 |a Neoplasms: genetics
|2 MeSH
650 _ 2 |a Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Neoplasms: pathology
|2 MeSH
650 _ 2 |a Oncogene Proteins: chemistry
|2 MeSH
650 _ 2 |a Oncogene Proteins: genetics
|2 MeSH
650 _ 2 |a Oncogene Proteins: metabolism
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Protein Domains
|2 MeSH
650 _ 2 |a Protein Structure, Secondary
|2 MeSH
650 _ 2 |a Protein Tyrosine Phosphatases: chemistry
|2 MeSH
650 _ 2 |a Protein Tyrosine Phosphatases: genetics
|2 MeSH
650 _ 2 |a Protein Tyrosine Phosphatases: metabolism
|2 MeSH
700 1 _ |a Oyenarte, Iker
|b 1
700 1 _ |a Hardy, Serge
|b 2
700 1 _ |a Breiderhoff, Tilman
|0 P:(DE-2719)9003035
|b 3
|u dzne
700 1 _ |a Stuiver, Marchel
|b 4
700 1 _ |a Kostantin, Elie
|b 5
700 1 _ |a Diercks, Tammo
|b 6
700 1 _ |a Pey, Angel L
|b 7
700 1 _ |a Ereño-Orbea, June
|b 8
700 1 _ |a Martínez-Chantar, María Luz
|b 9
700 1 _ |a Khalaf-Nazzal, Reham
|b 10
700 1 _ |a Claverie-Martin, Felix
|b 11
700 1 _ |a Müller, Dominik
|b 12
700 1 _ |a Tremblay, Michel L
|b 13
700 1 _ |a Martínez-Cruz, Luis Alfonso
|0 0000-0002-5856-9377
|b 14
773 _ _ |a 10.1074/jbc.M116.759944
|g Vol. 292, no. 3, p. 786 - 801
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|y 2017
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