InTP53-mutated MDS, the “multihit” involvement with other genomic or chromosomal alterations is observed [58].TP53copy-number loss is prevalent in 70% of AML cases with a concomitantTP53gene abnormality [32]. The recently investigated cohort of five hundred de novo and refractory AML patients...
5. L. S. Nguyenet al., Contribution of copy number variants involving nonsense-mediated mRNA decay pathway genes to neuro-developmental disorders.Hum Mol Genet22, 1816-1825 (2013). 6. F. Laumonnieret al., Mutation...
Despite the frequent use of mouse models for the study of p53 [7,8,9], there has been a lack of information that address common and divergent parts of the p53 gene regulatory network (GRN) between mice and humans. There is evidence that gene expression and underlying regulatory programs hav...
Definition of promoters and enhancers Gene promoters were defined as regions spanning 1000 base pairs upstream and 200 base pairs downstream from their transcriptional start site. Ensembl gene annotation GRCh37 release 87 was used to define transcriptional start sites. To define enhancers, we first ide...
Interestingly, in mES cells p53 is able to regulate gene transcription through binding to the enhancers far from the gene body [59]. This opens up a new avenue to study the transcriptional regulation, particularly repression, by p53. In mES cells, in response to DNA damage, p53 represses ...
The TP53 gene has a significant frequency of alteration in human cancers, which is associated with a high rate of tumor progression in an uncontrolled way. Li-Fraumeni syndrome has the possibility of a variety of early-onset cancers, which the underlying cause is those germline mutations [1]....
We have defined Li-Fraumeni-like families (LFL) as having at least two relatives affected with the tumors in the extended definition of LFS, but not fulfilling the classical definition. We analyzed exons in 1 through 11 of the p53 gene from blood DNA from affected individuals in 53 LFL ...
1. p53—The Gene, the Protein, and the Isoforms The tumor-suppressor protein p53 has been named the ‘guardian of the genome’ [1], as well as the ‘coordinator of the underlying processes of the hallmarks of cancer’ [2]. This is because its inactivation paves the way for cancers. ...
Quantitative Analysis of Residual Folding and DNA Binding in Mutant P53 Core Domain: Definition of Mutant States for Rescue in Cancer Therapy. Oncogene 2000, 19, 1245–1256. [Google Scholar] [CrossRef] [Green Version] Joerger, A.C.; Fersht, A.R. Structural Biology of the Tumor Suppressor ...
p53是一种肿瘤抑制基因(tumor suppressor gene)。在所有恶性肿瘤中,50%以上会出现该基因的突变。由这种基因编码的蛋白质(protein)是一种转录因子(transcriptional factor),其控制着细胞周期的启动。许多有关细胞健康的信号向p53蛋白发送。关于是否开始细胞分裂就由这个蛋白决定。如果这个细胞受损,又不能得到修复,则p53蛋...