Liu D X, Greene L A
Department of Pathology, Taub Center for Alzheimer's Disease Research, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Neuron. 2001 Nov 8;32(3):425-38. doi: 10.1016/s0896-6273(01)00495-0.
Neuronal death induced by a variety of means requires participation of the E2F family of transcription factors. Here, we show that E2F acts as a gene silencer in neurons and that repression of E2F-responsive genes is required for neuronal survival. Moreover, neuronal death evoked by DNA damaging agents or trophic factor withdrawal is characterized by derepression of E2F-responsive genes. Such derepression, rather than direct E2F-promoted gene activation, is required for death. Among the genes that are derepressed in neurons subjected to DNA damage or trophic factor withdrawal are the transcription factors B- and C-myb. Overexpression of B- and C-myb is sufficient to evoke neuronal death. These findings support a model in which E2F-dependent gene repression and derepression play pivotal roles in neuronal survival and death, respectively.
由多种方式诱导的神经元死亡需要转录因子E2F家族的参与。在此，我们表明E2F在神经元中作为一种基因沉默子发挥作用，并且抑制E2F反应性基因是神经元存活所必需的。此外，由DNA损伤剂或营养因子撤除引发的神经元死亡的特征是E2F反应性基因的去抑制。这种去抑制而非直接的E2F促进的基因激活是死亡所必需的。在遭受DNA损伤或营养因子撤除的神经元中去抑制的基因中，转录因子B-myb和C-myb是其中的一部分。B-myb和C-myb的过表达足以引发神经元死亡。这些发现支持了一种模型，即E2F依赖的基因抑制和去抑制分别在神经元存活和死亡中起关键作用。
