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

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...

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Autores principales: Hussain, Tabish, Lee, Jaeho, Abba, Martín Carlos, Chen, Junjie, Aldaz, Claudio Marcelo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/97255
https://ri.conicet.gov.ar/11336/81843
https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/full
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-97255
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
spellingShingle Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
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
topic_facet Bioquímica
Ciencias Naturales
Ciencias Exactas
Interactome
Metabolic pathways
Protein transport
Tap-ms
WW domains
WWOX
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.
format Articulo
Articulo
author Hussain, Tabish
Lee, Jaeho
Abba, Martín Carlos
Chen, Junjie
Aldaz, Claudio Marcelo
author_facet Hussain, Tabish
Lee, Jaeho
Abba, Martín Carlos
Chen, Junjie
Aldaz, Claudio Marcelo
author_sort Hussain, Tabish
title Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved
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
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/97255
https://ri.conicet.gov.ar/11336/81843
https://www.frontiersin.org/articles/10.3389/fonc.2018.00591/full
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