首页> 美国卫生研究院文献>The Journal of Neuroscience >BNIP3 (Bcl-2 19 kDa Interacting Protein) Acts as Transcriptional Repressor of Apoptosis-Inducing Factor Expression Preventing Cell Death in Human Malignant Gliomas
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BNIP3 (Bcl-2 19 kDa Interacting Protein) Acts as Transcriptional Repressor of Apoptosis-Inducing Factor Expression Preventing Cell Death in Human Malignant Gliomas

机译:BNIP3(Bcl-2 19 kDa相互作用蛋白)充当转录抑制因子诱导人恶性胶质瘤细胞死亡诱导细胞凋亡。

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摘要

The Bcl-2 19 kDa interacting protein (BNIP3) is a pro-cell-death BH3-only member of the Bcl-2 family. We previously found that BNIP3 is localized to the nucleus in the majority of glioblastoma multiforme (GBM) tumors and fails to induce cell death. Herein, we have discovered that nuclear BNIP3 binds to the promoter of the apoptosis-inducing factor (AIF) gene and represses its expression. BNIP3 associates with PTB-associating splicing factor (PSF) and HDAC1 (histone deacetylase 1) contributing to transcriptional repression of the AIF gene. This BNIP3-mediated reduction in AIF expression leads to decreased temozolomide-induced apoptosis in glioma cells. Furthermore, nuclear BNIP3 expression in GBMs correlates with decreased AIF expression. Together, we have discovered a novel transcriptional repression function for BNIP3 causing reduced AIF expression and increased resistance to apoptosis. Thus, nuclear BNIP3 may confer a survival advantage to glioma cells and explain, in part, why BNIP3 is expressed at high levels in solid tumors, especially GBM.
机译:Bcl-2 19 kDa相互作用蛋白(BNIP3)是Bcl-2家族中一个仅死于细胞的BH3成员。我们先前发现BNIP3定位于大多数胶质母细胞瘤(GBM)肿瘤的细胞核中,并且无法诱导细胞死亡。在这里,我们发现核BNIP3绑定到凋亡诱导因子(AIF)基因的启动子,并抑制其表达。 BNIP3与PTB相关剪接因子(PSF)和HDAC1(组蛋白脱乙酰基酶1)相关,有助于AIF基因的转录抑制。 BNIP3介导的AIF表达减少导致胶质瘤细胞中替莫唑胺诱导的细胞凋亡减少。此外,GBM中的核B​​NIP3表达与AIF表达降低有关。在一起,我们发现了BNIP3的新型转录抑制功能,导致减少的AIF表达和增加的抗凋亡能力。因此,核BNIP3可能赋予神经胶质瘤细胞生存优势,并部分解释为什么BNIP3在实体瘤尤其是GBM中高水平表达。

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