F-box proteins: Keeping the epithelial-to-mesenchymal transition (EMT) in check.
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.
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: victor.diaz@upf.edu.
Víctor M
VM
Díaz
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: agarcia@imim.es.
Antonio García
AG
de Herreros
D000818:Animals; D044842:Cullin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism
C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000071250:Snail Family Transcription Factors; C493170:TRIB1 protein, human; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases
Cancer; EMT; F-box; Proteasome; Snail; Twist; Ubiquitination; Zeb