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dc.contributor.author
Hussain, Tabish
dc.contributor.author
Lee, Jaeho
dc.contributor.author
Abba, Martín Carlos
dc.contributor.author
Chen, Junjie
dc.contributor.author
Aldaz, Claudio Marcelo
dc.date.available
2019-08-20T19:07:35Z
dc.date.issued
2018-12
dc.identifier.citation
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
dc.identifier.issn
2234-943X
dc.identifier.uri
http://hdl.handle.net/11336/81843
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media SA
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Interactome
dc.subject
Metabolic Pathways
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Protein Transport
dc.subject
Tap-Ms
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Ww Domains
dc.subject
Wwox
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry: Identification of top interactors and key metabolic pathways involved
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-08-08T16:05:25Z
dc.journal.volume
8
dc.journal.pagination
1-14
dc.journal.pais
Suiza
dc.journal.ciudad
Lausana
dc.description.fil
Fil: Hussain, Tabish. University of Texas; Estados Unidos
dc.description.fil
Fil: Lee, Jaeho. University of Texas; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Chen, Junjie. University of Texas; Estados Unidos
dc.description.fil
Fil: Aldaz, Claudio Marcelo. University of Texas; Estados Unidos
dc.journal.title
Frontiers in Oncology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fonc.2018.00591
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/full
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