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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/81843
Ver los metadatos del registro completo
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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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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