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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/97255
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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 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 |
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article |
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publishedVersion |
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http://sedici.unlp.edu.ar/handle/10915/97255 |
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dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
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http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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