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凋亡相关的早幼粒细胞白血病锌指蛋白(PLZF)靶基因的鉴定

Identification of apoptosis-related PLZF target genes.

作者信息

Bernardo Maria Victoria, Yelo Estefanía, Gimeno Lourdes, Campillo José Antonio, Parrado Antonio

机构信息

Servicio de Inmunología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.

出版信息

Biochem Biophys Res Commun. 2007 Jul 27;359(2):317-22. doi: 10.1016/j.bbrc.2007.05.085. Epub 2007 May 24.

Abstract

The PLZF gene encodes a BTB/POZ-zinc finger-type transcription factor, involved in physiological development, proliferation, differentiation, and apoptosis. In this paper, we investigate proliferation, survival, and gene expression regulation in stable clones from the human haematopoietic K562, DG75, and Jurkat cell lines with inducible expression of PLZF. In Jurkat cells, but not in K562 and DG75 cells, PLZF induced growth suppression and apoptosis in a cell density-dependent manner. Deletion of the BTB/POZ domain of PLZF abrogated growth suppression and apoptosis. PLZF was expressed with a nuclear speckled pattern distinctively in the full-length PLZF-expressing Jurkat clones, suggesting that the nuclear speckled localization is required for PLZF-induced apoptosis. By microarray analysis, we identified that the apoptosis-inducer TP53INP1, ID1, and ID3 genes were upregulated, and the apoptosis-inhibitor TERT gene was downregulated. The identification of apoptosis-related PLZF target genes may have biological and clinical relevance in cancer typified by altered PLZF expression.

摘要

PLZF基因编码一种BTB/POZ-锌指型转录因子,参与生理发育、增殖、分化和凋亡过程。在本文中,我们研究了来自人造血K562、DG75和Jurkat细胞系的稳定克隆中PLZF可诱导表达情况下的增殖、存活及基因表达调控。在Jurkat细胞中,而非K562和DG75细胞中,PLZF以细胞密度依赖性方式诱导生长抑制和凋亡。PLZF的BTB/POZ结构域缺失消除了生长抑制和凋亡作用。在全长PLZF表达的Jurkat克隆中,PLZF以独特的核斑点模式表达,提示核斑点定位是PLZF诱导凋亡所必需的。通过微阵列分析,我们发现凋亡诱导因子TP53INP1、ID1和ID3基因上调,而凋亡抑制因子TERT基因下调。凋亡相关PLZF靶基因的鉴定可能在以PLZF表达改变为特征的癌症中具有生物学和临床意义。

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