F-box proteins: Keeping the epithelial-to-mesenchymal transition (EMT) in check

Víctor M Díaz; Antonio García de Herreros

doi:10.1016/j.semcancer.2015.10.003

F-box proteins: Keeping the epithelial-to-mesenchymal transition (EMT) in check

Semin Cancer Biol. 2016 Feb:36:71-9. doi: 10.1016/j.semcancer.2015.10.003. Epub 2015 Nov 11.

Authors

Víctor M Díaz¹, Antonio García de Herreros²

Affiliations

¹ Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; Parc de Recerca Biomèdica de Barcelona, Doctor Aiguader, 88, E-08003 Barcelona, Spain. Electronic address: [email protected].
² Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; Parc de Recerca Biomèdica de Barcelona, Doctor Aiguader, 88, E-08003 Barcelona, Spain. Electronic address: [email protected].

PMID: 26506454
DOI: 10.1016/j.semcancer.2015.10.003

Abstract

F-box proteins are the key recognition subunit of multimeric E3 ubiquitin ligase complexes that participate in the proteasome degradation of specific substrates. In the last years, a discrete number of F-box proteins have been shown to regulate the epithelial-to-mesenchymal transition (EMT), a process defined by a rapid change of cell phenotype, the loss of epithelial characteristics and the acquisition of a more invasive phenotype. Specific EMT transcription factors (EMT-TFs), such as Snail, Slug, Twist and Zeb, control EMT induction both during development and in cancer. These EMT-TFs are short-lived proteins that are targeted to the proteasome system by specific F-box proteins, keeping them at low levels. F-box proteins also indirectly regulate the EMT process by controlling EMT inducers, such as Notch, c-Myc or mTOR. Here we summarize the role that these F-box proteins (Fbxw1, Fbxw7, Fbxl14, Fbxl5, Fbxo11 and Fbxo45) play in controlling EMT during development and cancer progression, a process dependent on post-translational modifications that govern their interaction with target proteins.

Keywords: Cancer; EMT; F-box; Proteasome; Snail; Twist; Ubiquitination; Zeb.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cullin Proteins / chemistry
Cullin Proteins / genetics
Cullin Proteins / metabolism
Epithelial-Mesenchymal Transition / genetics*
F-Box Proteins / genetics*
F-Box Proteins / metabolism*
Gene Expression Regulation
Humans
Intracellular Signaling Peptides and Proteins / chemistry
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Multiprotein Complexes
Neoplasms / etiology
Neoplasms / metabolism
Protein Binding
Protein Interaction Domains and Motifs
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / chemistry
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Snail Family Transcription Factors / metabolism
Twist-Related Protein 1 / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

Cullin 1
Cullin Proteins
F-Box Proteins
Intracellular Signaling Peptides and Proteins
Multiprotein Complexes
Snail Family Transcription Factors
TRIB1 protein, human
Twist-Related Protein 1
ZEB1 protein, human
Zinc Finger E-box-Binding Homeobox 1
Ubiquitin-Protein Ligases
Protein Serine-Threonine Kinases