The TRAF-interacting protein (TRAIP) is a novel E2F target with peak expression in mitosis.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_CD436F3D40E0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The TRAF-interacting protein (TRAIP) is a novel E2F target with peak expression in mitosis.
Périodique
Oncotarget
Auteur(s)
Chapard C., Hohl D., Huber M.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
6
Numéro
25
Pages
20933-20945
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The TRAF-interacting protein (TRAIP) is an E3 ubiquitin ligase required for cell proliferation. TRAIP mRNA is downregulated in human keratinocytes after inhibition of the PI3K/AKT/mTOR signaling. Since E2F transcription factors are downstream of PI3K/AKT/mTOR we investigated whether they regulate TRAIP expression. E2F1 expression significantly increased the TRAIP mRNA level in HeLa cells. Reporter assays with the 1400 bp 5'-upstream promoter in HeLa cells and human keratinocytes showed that E2F1-, E2F2- and E2F4-induced upregulation of TRAIP expression is mediated by 168 bp upstream of the translation start site. Mutating the E2F binding site within this fragment reduced the E2F1- and E2F2-dependent promoter activities and protein-DNA complex formation in gel shift assays. Abundance of TRAIP mRNA and protein was regulated by the cell cycle with a peak in G2/M. Expression of GFP and TRAIP-GFP demonstrated that TRAIP-GFP protein has a lower steady-state concentration than GFP despite similar mRNA levels. Cycloheximide inhibition experiments indicated that the TRAIP protein has a half-life of around four hours. Therefore, the combination of cell cycle-dependent transcription of the TRAIP gene by E2F and rapid protein degradation leads to cell cycle-dependent expression with a maximum in G2/M. These findings suggest that TRAIP has important functions in mitosis and tumorigenesis.
Mots-clé
3T3 Cells, Animals, Cell Cycle, Cell Nucleus/metabolism, Cell Proliferation, Cycloheximide/chemistry, E2F1 Transcription Factor/metabolism, E2F2 Transcription Factor/metabolism, E2F4 Transcription Factor/metabolism, Gene Expression Regulation, Neoplastic, Green Fluorescent Proteins/metabolism, HEK293 Cells, HeLa Cells, Humans, Keratinocytes/cytology, Mice, Mitosis, Plasmids/metabolism, Promoter Regions, Genetic, Protein Biosynthesis, Protein Synthesis Inhibitors/chemistry, RNA, Messenger/metabolism, Ubiquitin-Protein Ligases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/10/2015 13:47
Dernière modification de la notice
20/08/2019 16:47
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