New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins

Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proli...

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Main Authors: Pilar Eraso, María J. Mazón, Victoria Jiménez, Patricia Pizarro-García, Eva P. Cuevas, Jara Majuelos-Melguizo, Jesús Morillo-Bernal, Amparo Cano, Francisco Portillo
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/11/4433
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author Pilar Eraso
María J. Mazón
Victoria Jiménez
Patricia Pizarro-García
Eva P. Cuevas
Jara Majuelos-Melguizo
Jesús Morillo-Bernal
Amparo Cano
Francisco Portillo
author_facet Pilar Eraso
María J. Mazón
Victoria Jiménez
Patricia Pizarro-García
Eva P. Cuevas
Jara Majuelos-Melguizo
Jesús Morillo-Bernal
Amparo Cano
Francisco Portillo
author_sort Pilar Eraso
collection DOAJ
description Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer. Moreover, LOXL2 is able to induce the epithelial-to-mesenchymal transition (EMT) process—the first step in the metastatic cascade. To uncover the underlying mechanisms of the great variety of functions of intracellular LOXL2, we carried out an analysis of LOXL2’s nuclear interactome. This study reveals the interaction of LOXL2 with numerous RNA-binding proteins (RBPs) involved in several aspects of RNA metabolism. Gene expression profile analysis of cells silenced for LOXL2, combined with in silico identification of RBPs’ targets, points to six RBPs as candidates to be substrates of LOXL2’s action, and that deserve a more mechanistic analysis in the future. The results presented here allow us to hypothesize novel LOXL2 functions that might help to comprehend its multifaceted role in the tumorigenic process.
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spelling doaj.art-7d4f76d2032740ee96f68f6682c11c5c2023-11-18T08:16:33ZengMDPI AGMolecules1420-30492023-05-012811443310.3390/molecules28114433New Functions of Intracellular LOXL2: Modulation of RNA-Binding ProteinsPilar Eraso0María J. Mazón1Victoria Jiménez2Patricia Pizarro-García3Eva P. Cuevas4Jara Majuelos-Melguizo5Jesús Morillo-Bernal6Amparo Cano7Francisco Portillo8Departamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainDepartamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, SpainLysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer. Moreover, LOXL2 is able to induce the epithelial-to-mesenchymal transition (EMT) process—the first step in the metastatic cascade. To uncover the underlying mechanisms of the great variety of functions of intracellular LOXL2, we carried out an analysis of LOXL2’s nuclear interactome. This study reveals the interaction of LOXL2 with numerous RNA-binding proteins (RBPs) involved in several aspects of RNA metabolism. Gene expression profile analysis of cells silenced for LOXL2, combined with in silico identification of RBPs’ targets, points to six RBPs as candidates to be substrates of LOXL2’s action, and that deserve a more mechanistic analysis in the future. The results presented here allow us to hypothesize novel LOXL2 functions that might help to comprehend its multifaceted role in the tumorigenic process.https://www.mdpi.com/1420-3049/28/11/4433LOXL2intracellular LOXL2nuclear interactomeRNA-binding proteinsEMT
spellingShingle Pilar Eraso
María J. Mazón
Victoria Jiménez
Patricia Pizarro-García
Eva P. Cuevas
Jara Majuelos-Melguizo
Jesús Morillo-Bernal
Amparo Cano
Francisco Portillo
New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
Molecules
LOXL2
intracellular LOXL2
nuclear interactome
RNA-binding proteins
EMT
title New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
title_full New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
title_fullStr New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
title_full_unstemmed New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
title_short New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins
title_sort new functions of intracellular loxl2 modulation of rna binding proteins
topic LOXL2
intracellular LOXL2
nuclear interactome
RNA-binding proteins
EMT
url https://www.mdpi.com/1420-3049/28/11/4433
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