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.
Fil: Hussain, Tabish. University of Texas; Estados Unidos
Fil: Lee, Jaeho. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Chen, Junjie. University of Texas; Estados Unidos
Fil: Aldaz, Claudio Marcelo. University of Texas; Estados Unidos
Materia
INTERACTOME
METABOLIC PATHWAYS
PROTEIN TRANSPORT
TAP-MS
WW DOMAINS
WWOX
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/81843

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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 MarceloINTERACTOMEMETABOLIC PATHWAYSPROTEIN TRANSPORTTAP-MSWW DOMAINSWWOXhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It 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.Fil: Hussain, Tabish. University of Texas; Estados UnidosFil: Lee, Jaeho. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Chen, Junjie. University of Texas; Estados UnidosFil: Aldaz, Claudio Marcelo. University of Texas; Estados UnidosFrontiers Media SA2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/81843Hussain, Tabish; Lee, Jaeho; Abba, Martín Carlos; Chen, Junjie; Aldaz, Claudio Marcelo; Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry: Identification of top interactors and key metabolic pathways involved; Frontiers Media SA; Frontiers in Oncology; 8; 12-2018; 1-142234-943XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00591info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:16Zoai:ri.conicet.gov.ar:11336/81843instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:02:16.983CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
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 INTERACTOME
METABOLIC PATHWAYS
PROTEIN TRANSPORT
TAP-MS
WW DOMAINS
WWOX
topic INTERACTOME
METABOLIC PATHWAYS
PROTEIN TRANSPORT
TAP-MS
WW DOMAINS
WWOX
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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.
Fil: Hussain, Tabish. University of Texas; Estados Unidos
Fil: Lee, Jaeho. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Chen, Junjie. University of Texas; Estados Unidos
Fil: Aldaz, Claudio Marcelo. University of Texas; Estados Unidos
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 2018-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/81843
Hussain, Tabish; Lee, Jaeho; Abba, Martín Carlos; Chen, Junjie; Aldaz, Claudio Marcelo; Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry: Identification of top interactors and key metabolic pathways involved; Frontiers Media SA; Frontiers in Oncology; 8; 12-2018; 1-14
2234-943X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/81843
identifier_str_mv Hussain, Tabish; Lee, Jaeho; Abba, Martín Carlos; Chen, Junjie; Aldaz, Claudio Marcelo; Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry: Identification of top interactors and key metabolic pathways involved; Frontiers Media SA; Frontiers in Oncology; 8; 12-2018; 1-14
2234-943X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2018.00591
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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