HDAC-3 participates in the repression of e2f-dependent gene transcription in primary differentiated neurons

被引:18
作者
Panteleeva, I [1 ]
Rouaux, C [1 ]
Larmet, Y [1 ]
Boutillier, S [1 ]
Loeffler, JP [1 ]
Boutillier, AL [1 ]
机构
[1] Fac Med, EA3433, Lab Signalisat Mol & Neurodegenerescence, F-67085 Strasbourg, France
来源
SIGNAL TRANSDUCTION PATHWAYS, CHROMATIN STRUCTURE, AND GENE EXPRESSION MECHANISMS AS THERAPEUTIC TARGETS | 2004年 / 1030卷
关键词
HDAC; E2F-dependent transcription; caspase; neuronal apoptosis;
D O I
10.1196/annals.1329.076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of e2f-1 gene expression is an event that has been now established in many models of neuronal apoptosis. Accumulated E2F-1 protein has also been observed in post mortem brains obtained from patients suffering from different neurodegenerative diseases. We have previously shown in primary neuronal cultures that e2f-1 gene transcription was actively repressed in neuroprotective conditions through HDAC-dependent regulation on the E2F-responsive elements (E2F-REs) located in the e2f-1 gene promoter. Here, we further investigated the protein complex bound to these sites by gel shift analysis. We found that the specific protein binding to E2F-REs is altered in apoptotic conditions compared to neuroprotective conditions, suggesting that the proteic constituents of the complex are likely to be modified upon apoptosis onset. Indeed, Western blot analysis showed a time-dependent degradation of the Rb/E2F binding protein HDAC-3 during apoptosis, a degradation that is caspase-dependent. Altogether, these data point to HDAC-3 as a good candidate involved in the active e2f-1 repression necessary for neuroprotection.
引用
收藏
页码:656 / 660
页数:5
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