Reference : The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in e...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/133423
The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells.
English
Turtoi, Andrei mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Mottet, Denis mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Matheus, Nicolas [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Dumont, Bruno mailto [Université de Liège - ULg > > > GIGA - Membres]
Peixoto, Paul mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Hennequière, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Deroanne, Christophe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
Colige, Alain mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
De Pauw, Edwin mailto [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
Bellahcene, Akeila mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
2012
Angiogenesis
Kluwer Academic Publishers
Yes (verified by ORBi)
International
0969-6970
Dordrecht
The Netherlands
[en] vascular biology ; proteomics ; gene regulation ; STAT3
[en] Histone deacetylases (HDACs) are a family of 18 enzymes that deacetylate lysine residues of both histone and nonhistone proteins and to a large extent govern the process of angiogenesis. Previous studies have shown that specific inhibition of HDAC7 blocks angiogenesis both in vitro and in vivo. However, the underlying molecular mechanisms are not fully understood and hence preclude any meaningful development of suitable therapeutic modalities. The goal of the present study was to further the understanding of HDAC7 epigenetic control of angiogenesis in human endothelial cells using the proteomic approach. The underlying problem was approached through siRNA-mediated gene-expression silencing of HDAC7 in human umbilical vein endothelial cells (HUVECs). To this end, HUVEC proteins were extracted and proteomically analyzed. The emphasis was placed on up-regulated proteins, as these may represent potential direct epigenetic targets of HDAC7. Among several proteins, A-kinase anchor protein 12 (AKAP12) was the most reproducibly up-regulated protein following HDAC7 depletion. This overexpression of AKAP12 was responsible for the inhibition of migration and tube formation in HDAC7-depleted HUVEC. Mechanistically, H3 histones associated with AKAP12 promoter were acetylated following the removal of HDAC7, leading to an increase in its mRNA and protein levels. AKAP12 is responsible for protein kinase C mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3). Phosphorylated STAT3 increasingly binds to the chromatin and AKAP12 promoter and is necessary for maintaining the elevated levels of AKAP12 following HDAC7 knockdown. We demonstrated for the first time that AKAP12 tumor/angiogenesis suppressor gene is an epigenetic target of HDAC7, whose elevated levels lead to a negative regulation of HUVEC migration and inhibit formation of tube-like structures.
Giga-Cancer
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; REGION WALLONNE : NEO-ANGIO ; Centre Anti-Cancéreux ; Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA ; TELEVIE
http://hdl.handle.net/2268/133423
10.1007/s10456-012-9279-8

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
(176) TURTOI A ANGIOGENESIS 2012.pdfPublisher postprint754.86 kBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.