Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_7C8A78A053FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity.
Périodique
Oncotarget
Auteur(s)
Oikonomaki M., Bady P., Hegi M.E.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
15/12/2017
Peer-reviewed
Oui
Volume
8
Numéro
66
Pages
110490-110502
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Expression based prediction of new genomic alterations in glioblastoma identified the de-ubiquitinase Ubiquitin Specific Peptidase 15 ( javax.xml.bind.JAXBElement@31cce702 ) as potential tumor suppressor gene associated with genomic deletions (11%). Ectopic expression of USP15 in glioblastoma cell-lines reduced colony formation and growth in soft agar, while overexpression of its functional mutant had the opposite effect. Evaluation of the protein binding network of USP15 by Mass Spectrometry in glioblastoma cells uncovered eight novel interacting proteins, including HECT Domain Containing E3 Ubiquitin Protein Ligase 1 (HECTD1), whose mouse homologue has been associated with an inhibitory effect on the WNT-pathway. USP15 de-ubiquitinated and thereby stabilized HECTD1 in glioblastoma cells, while depletion of USP15 led to decreased HECTD1 protein levels. Expression of USP15 in glioblastoma cells attenuated WNT-pathway activity, while expression of the functional mutant enhanced the activity. Modulation of HECTD1 expression pheno-copied the effects observed for USP15. In accordance, human glioblastoma display a weak but significant negative correlation between javax.xml.bind.JAXBElement@31337d24 and javax.xml.bind.JAXBElement@560c9774 expression. Taken together, the data provide evidence that USP15 attenuates the canonical WNT pathway mediated by stabilization of HECTD1, supporting a tumor suppressing role of USP15 in a subset of glioblastoma.

Mots-clé
HECTD1, USP15, WNT pathway, glioblastoma, tumor suppressor
Pubmed
Web of science
Création de la notice
22/01/2018 18:12
Dernière modification de la notice
20/08/2019 15:38
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