Identification and classification of p53-regulated genes
Identification and classification of p53-regulated genes
复制标题
DOI：
10.1073/pnas.96.25.14517
复制
发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Yu, J;Zhang, L;Vogelstein, B
p53的序列特异性转激活对其作为肿瘤抑制因子的作用至关重要。我们建立了一个改良的四环素诱导系统来寻找p53诱导后很快被激活的转录本。通过基因表达序列分析鉴定出的9954个独特转录本中，有34个扩增了10倍以上；其中31种以前不知道是由p53调节的。这些基因的转录模式，以及先前描述的p53调控基因，在一组广泛研究的结直肠癌细胞系中进行了评估和分类。“I类”基因在所有细胞系中均被p53诱导；“II类”基因在部分品系中被诱导；和“III类”基因没有在任何品系中被诱导。这些基因还通过诱导的时间、临床相关化疗药物的诱导、这种诱导对p53的绝对要求以及p53的同源物p73的诱导性来区分。结果显示p53的转录反应存在实质性的异质性。甚至在来源于单一上皮细胞类型的细胞中，为更深入地了解p53肿瘤抑制作用铺平了道路。
Sequence-specific transactivation by p53 is essential to its role as a tumor suppressor. A modified tetracycline-inducible system was established to search for transcripts that were activated soon after p53 induction. Among 9,954 unique transcripts identified by serial analysis of gene expression, 34 were increased more than 10-fold; 31 of these had not previously been known to be regulated by p53. The transcription patterns of these genes, as well as previously described p53-regulated genes, were evaluated and classified in a panel of widely studied colorectal cancer cell lines. "Class I" genes were uniformly induced by p53 in all cell lines; "class II" genes were induced in a subset of the lines; and "class III" genes were not induced in any of the lines. These genes were also distinguished by the timing of their induction, their induction by clinically relevant chemotherapeutic agents, the absolute requirement for p53 in this induction, and their inducibility by p73, a p53 homolog. The results revealed substantial heterogeneity in the transcriptional responses to p53. even in cells derived from a single epithelial cell type, and pave the way to a deeper understanding of p53 tumor suppressor action.