The tumor suppressive transcription factor p53 is frequently inactivated in cancer cells by missense mutations that cluster in the DNA binding domain. 30% hit mutational hotspot residues, resulting in a complete loss of transcriptional activity and mutan
p53 参与了恶性肿瘤进展中的所有编排过程,因此被称为癌症的“全能选手”。 p53 作为一种同源四聚体转录因子,其突变类型分为 三种:功能丧失(loss of function, LOF)、显性阴性(dominant negative, DN) 和功能获得(gain-of-function, GOF)。...
What the papers say: p53 Loss of Function: Implications for the Processes of Immortalization and Tumorigenesis (p 557-560)The complex process of cell immortalization and transformation is likely to involve the inactivation of growth regulatory genes. Mutations (deletions, missense mutations) in the ...
Loss of function and p53 protein stabilization. Wild-type (wt) p53 protein is rapidly degraded, has a short half-life and low intracellular levels. Stabilization of wt p53 protein following an appropriat... Blagosklonny,V Mikhail - 《Oncogene》 被引量: 280发表: 1997年 Loss of function and...
Research in animal models and in human patients has demonstrated that altered expression of the deiodinases and mutations or loss of function of THRs are common events in some tumors and can affect cancer cell proliferation, invasiveness, and angiogenesis3,9,10,11,12. Moreover, recent evidence ...
A large body of evidence supports the importance of these activities for p53 function, including recent studies showing that substitution of a gene encoding a transcriptionally inactive mutant p53 for the wild-type gene in mice leads to loss of growth inhibitory activity 3•., 4•.. Despite ...
在肿瘤中,p53失活突变多发生在DBD中,突变破坏p53与其靶DNA序列的结合能力,从而阻滞靶基因的转录激活,是 loss-of-function 突变。其他特殊功能异常发生取决于TP53基因突变的类型和位置。p53不同的突变方式对应的免疫组化表达模式 正常: --p53正常/野生型(abnormal or wild type pattern):低-中等不均匀的核阳性(2020...
A loss-of-function mutation in def confers hypoplastic digestive organs and selectively up-regulates the expression of Δ113p53, counterpart to a newly identified isoform of p53 produced by an alternative internal promoter in intron 4 of the p53 gene in human. The increased Δ113p53 expression ...
这些突变不仅抑制了wtp53 (wild-type p53)的抗癌活性,也可能具有获得性癌症驱动活性(GOF activity, gain-of-function activities),还潜在调控肿瘤微环境TME (tumour microenvironment)。靶向p53(或增强wtp53活性,或抑制TP53突变)具备肿瘤治疗的普适性,具有“一靶多癌,一劳永逸”的应用前景。
Although we have reported that mutant p53 causes chemotherapy resistance due to loss of function of inactivating PUMA transcription [41], it is suggested that we should also explore gain of function with mutant p53. Previous studies add to these results suggesting that AKT inhibitors have the ...