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@ARTICLE{GimnezMascarell:276852,
author = {Giménez-Mascarell, Paula and Oyenarte, Iker and Hardy,
Serge and Breiderhoff, Tilman and Stuiver, Marchel and
Kostantin, Elie and Diercks, Tammo and Pey, Angel L and
Ereño-Orbea, June and Martínez-Chantar, María Luz and
Khalaf-Nazzal, Reham and Claverie-Martin, Felix and Müller,
Dominik and Tremblay, Michel L and Martínez-Cruz, Luis
Alfonso},
title = {{S}tructural {B}asis of the {O}ncogenic {I}nteraction of
{P}hosphatase {PRL}-1 with the {M}agnesium {T}ransporter
{CNNM}2.},
journal = {JBC papers in press},
volume = {292},
number = {3},
issn = {0021-9258},
address = {Bethesda, MD},
publisher = {American Soc. for Biochemistry and Molecular Biology},
reportid = {DZNE-2025-00365},
pages = {786 - 801},
year = {2017},
note = {ISSN 0021-9258 not unique: **2 hits**.},
abstract = {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.},
keywords = {Animals / Cation Transport Proteins: chemistry / Cation
Transport Proteins: genetics / Cation Transport Proteins:
metabolism / Immediate-Early Proteins: chemistry /
Immediate-Early Proteins: genetics / Immediate-Early
Proteins: metabolism / Magnesium: chemistry / Magnesium:
metabolism / Mice / Neoplasm Metastasis / Neoplasms:
genetics / Neoplasms: metabolism / Neoplasms: pathology /
Oncogene Proteins: chemistry / Oncogene Proteins: genetics /
Oncogene Proteins: metabolism / Protein Binding / Protein
Domains / Protein Structure, Secondary / Protein Tyrosine
Phosphatases: chemistry / Protein Tyrosine Phosphatases:
genetics / Protein Tyrosine Phosphatases: metabolism /
PRL-1, CNNM2, CBS domain (Other) / cancer (Other) / cell
proliferation (Other) / magnesium (Other) / phosphatase
(Other) / transporter (Other) / Cation Transport Proteins
(NLM Chemicals) / Cnnm2 protein, mouse (NLM Chemicals) /
Immediate-Early Proteins (NLM Chemicals) / Oncogene Proteins
(NLM Chemicals) / Protein Tyrosine Phosphatases (NLM
Chemicals) / Ptp4a1 protein, mouse (NLM Chemicals) /
Magnesium (NLM Chemicals)},
ddc = {610},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27899452},
pmc = {pmc:PMC5247653},
doi = {10.1074/jbc.M116.759944},
url = {https://pub.dzne.de/record/276852},
}