论文部分内容阅读
Damage-regulated autophagy modulator1 (DRAM1),a novel TP53 target gene,is an evolutionarily conserved lysosomal protein and plays an essential role in TP53-dependent autophagy activation and apoptosis (Crighton et al,2006).However,the mechanisms by which DRAM1 promotes autophagy and apoptosis are not clear.3-Nitropropionic acid (3-NP) is an inhibitor of mitochondrial respiratory complex Ⅱ.Intrastriatal administration of 3-NP produces neuropathology resemble to Huntington disease.3-NP-induced neuronal death was involved in autophagy and apoptosis.In vitro studies with 3-NP in TP53 wt and null cells,3-NP or CCCP increased the protein levels of DRAM1 in a TP53-dependent or independent manner.DRAM1 induction contributed to 3-NP-induced autophagy activation.Knock-down of DRAM1 with siRNA inhibited the activity of Ⅴ-ATPase,acidification of lysosomes and activation of lysosomal proteases.Knock-down of DRAM1 reduced the clearance of autophagososmes.