Regulation of neuron survival and death by p130 and associated chromatin modifiers (Gene Dev, 2005, 19:719-732)

報告日期: 2006/05/12
報告時間: 17:10/18:00
報告學生: 莊健盈
講評老師: 陳淑姿
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Regulation of neuron survival and death by p130 and associated chromatin modifiers

David X. Liu, Niharika Nath, Srikumar P. Chellappan, and Lloyd A. Greene

 

Speaker: 莊健盈                 Time: 12/5/2005 17:10~18:10

Commentator: 陳淑姿老師         Place: Room 602

 

Abstract:

   E2F acts as a gene silencer in neurons and that the 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. However, the key molecules involved in such regulation and the mechanisms by which they respond to apoptotic stimuli are largely unknown. The author first determined that p130 is the predominant Rb family member in neuronal E2F4-containing complexes and that loss of p130 or its displacement from such complexes led to E2F4 derepression and apoptosis. Moreover, The p130–E2F4 complex recruits the chromatin modifiers HDAC1 and Suv39H1 to promote gene silencing and neuron survival. Apoptotic stimuli induces neuron death by sequentially causing p130 hyperphosphorylation, dissociation of p130–E2F4–Suv39H1–HDAC complexes, altered modification of H3 histone and gene derepression. Taken together, these results demonstrate the major role of p130 in regulating neuron survival by tethering the corepressors, HDAC1 and Suv39H1, to E2F4-binding promoters.

 

References:

1.    Dyson, N. (1998) Genes Dev 12, 2245-2262

2.    Greene, L. A., Biswas, S. C., and Liu, D. X. (2004) Cell Death Differ 11, 49-60

3.    Liu, D. X., and Greene, L. A. (2001) Neuron 32, 425-438