Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved

Autores
Hussain, Tabish; Lee, Jaeho; Abba, Martín Carlos; Chen, Junjie; Aldaz, Claudio Marcelo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/97255

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spelling Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involvedHussain, TabishLee, JaehoAbba, Martín CarlosChen, JunjieAldaz, Claudio MarceloBioquímicaCiencias NaturalesCiencias ExactasInteractomeMetabolic pathwaysProtein transportTap-msWW domainsWWOXIt has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicadas2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1-14http://sedici.unlp.edu.ar/handle/10915/97255enginfo:eu-repo/semantics/altIdentifier/url/https://ri.conicet.gov.ar/11336/81843info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/fullinfo:eu-repo/semantics/altIdentifier/issn/2234-943Xinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00591info:eu-repo/semantics/altIdentifier/hdl/11336/81843info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:20:26Zoai:sedici.unlp.edu.ar:10915/97255Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:20:27.063SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
title Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
spellingShingle Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
Hussain, Tabish
Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
title_short Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
title_full Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
title_fullStr Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
title_full_unstemmed Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
title_sort Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
dc.creator.none.fl_str_mv Hussain, Tabish
Lee, Jaeho
Abba, Martín Carlos
Chen, Junjie
Aldaz, Claudio Marcelo
author Hussain, Tabish
author_facet Hussain, Tabish
Lee, Jaeho
Abba, Martín Carlos
Chen, Junjie
Aldaz, Claudio Marcelo
author_role author
author2 Lee, Jaeho
Abba, Martín Carlos
Chen, Junjie
Aldaz, Claudio Marcelo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
topic Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
dc.description.none.fl_txt_mv It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/full
info:eu-repo/semantics/altIdentifier/issn/2234-943X
info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00591
info:eu-repo/semantics/altIdentifier/hdl/11336/81843
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
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