PML colocalizes和稳定蛋白质TopBP1 DNA损伤反应。
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徐ZX Timanova-Atanasova,赵常KS RX
PML colocalizes和稳定蛋白质TopBP1 DNA损伤反应。
摩尔细胞杂志。2003年6月23日(12):4247 - 56。
- PubMed ID
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12773567 (在PubMed]
- 文摘
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PML肿瘤抑制基因不断被t(15、17)在急性早幼粒细胞白血病患者。早幼粒细胞白血病蛋白质(PML)是一种多功能蛋白,在细胞生长调控中扮演重要作用,细胞凋亡,转录调控、基因组的稳定性。我们的研究显示,PML colocalizes和同事体内蛋白质与DNA损伤反应TopBP1对电离辐射(IR)。与IR-induced PML和TopBP1与溴脱氧尿苷单链DNA疫源地。PML和TopBP1也与Rad50 Brca1,自动取款机,Rad9, BLM。红外光谱和干扰素(IFN) coinduce TopBP1和PML的表达水平。在PML-deficient NB4细胞,TopBP1无法形成IR-induced疫源地。All-trans-retinoic酸诱导重组PML核体(NB)和再现的IR-induced TopBP1疫源地。抑制PML蛋白表达的siRNA与显著降低TopBP1表达式。此外,TopBP1 PML-deficient细胞表达水平低,不能由红外或干扰素诱导表达。 Adenovirus-mediated overexpression of PML in PML(-/-) mouse embryo fibroblasts substantially increased TopBP1 expression, which colocalized with the PML NBs. These studies demonstrated a mechanism of PML-dependent expression of TopBP1. PML overexpression induced TopBP1 protein but not the mRNA expression. Pulse-chase labeling analysis demonstrated that PML overexpression stabilized the TopBP1 protein, suggesting that PML plays a role in regulating the stability of TopBP1 in response to IR. Together, our findings demonstrate that PML regulates TopBP1 functions by association and stabilization of the protein in response to IR-induced DNA damage.