Reference : The homeobox protein MSX2 interacts with tax oncoproteins and represses their transactiv...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/32308
The homeobox protein MSX2 interacts with tax oncoproteins and represses their transactivation activity.
English
Twizere, Jean-Claude mailto [Université de Liège - ULg > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech >]
Lefebvre, Laurent [> > > >]
Collete, Delphine [> > > >]
Debacq, Christophe [> > > >]
Urbain, Patrice [> > > >]
Heremans, Hubertine [> > > >]
Jauniaux, Jean-Claude [> > > >]
Burny, Arsene [> > > >]
Willems, Luc mailto [Université de Liège - ULg > > GIGA-Research - Gembloux Agro-Bio Tech >]
Kettmann, Richard mailto [Université de Liège - ULg > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech >]
2005
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
280
33
29804-11
Yes (verified by ORBi)
International
0021-9258
1083-351X
Baltimore
MD
[en] Activating Transcription Factor 4 ; DNA-Binding Proteins/physiology ; Gene Products, tax/physiology ; Hela Cells ; Homeodomain Proteins ; Human T-lymphotropic virus 1/physiology ; Humans ; Leukemia Virus, Bovine/physiology ; Repressor Proteins/physiology ; Trans-Activators/physiology ; Transcription Factors/physiology ; Transcription Factors, TFII/physiology
[en] Bovine leukemia virus (BLV) tax is an essential gene involved in the transcriptional activation of viral expression. Tax is also believed to be implicated in leukemogenesis because of its ability to immortalize primary cells in vitro. To gain insight into the molecular pathways mediating the activities of this important gene, we identified cellular proteins interacting with Tax. By means of a two-hybrid approach, we show that Tax specifically interacts with MSX2, a general repressor of gene expression. GST pull-down experiments and co-immunoprecipitation assays further confirmed binding specificity. Furthermore, the N-terminal residues 1-79 of MSX2 are required for binding, whereas the C-terminal residues 201-267 of MSX2 do not play a critical role. Whereas the oncogenic potential of Tax in primary cells was only slightly affected by overexpression of MSX2, the other function of Tax, namely LTR-dependent transcriptional activation, was inhibited by MSX2 in human HeLa and bovine B-lymphoblastoid (BL3) cell lines. This MSX2 repression function can be counteracted by overexpression of transcription factors CREB2 and RAP74. The Tax/MSX2 interplay thus results in repression of viral transcriptional activation possibly acting as a regulatory feedback loop. Importantly, this viral gene silencing is not strictly associated with a concomitant loss of Tax oncogenicity as measured by its ability to immortalize primary cells. And interestingly, MSX2 also interacts with and inhibits the transactivation function of the related Tax1 protein encoded by the Human T-cell leukemia virus type 1 (HTLV-1).
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/32308
also: http://hdl.handle.net/2268/35209 ; http://hdl.handle.net/2268/10586
10.1074/jbc.M503674200

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
Twizere et al 2005.pdfPublisher postprint314.44 kBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.