HDAC4 inhibits cell-cycle progression and protects neurons from cell death.

摘要: HDAC4 is a Class II histone deacetylase (HDAC) that highly expressed in the brain, but whose functional significance brain not known. We show forced expression of cerebellar granule neurons protects them against low potassium-induced apoptosis. also HT22 neuroblastoma cells from death induced by oxidative stress. HDAC4-mediated neuroprotection does require its HDAC catalytic domain and cannot be inhibited chemical inhibitors HDACs. Neuroprotection Raf-MEK-ERK or PI-3 kinase-Akt signaling pathways occurs despite activation c-jun, an event generally believed to condemn die. The protective action nucleus mediated region contains nuclear localization signal. inhibits activity cyclin-dependent kinase-1 (CDK1) progression proliferating HEK293T through cell cycle. Mice-lacking have elevated CDK1 display abnormalities including progressive loss Purkinje postnatally posterior lobes. Surviving these lobes duplicated soma. Furthermore, large numbers within affected incorporate BrdU, indicating cell-cycle progression. These along with ability inhibit cultured suggest preventing abortive