29. Bullock, A.N. and A.R. Fersht,Rescuing the function of mutant p53.Nat Rev Cancer, 2001. 1(1): p. 68-76. 30. Joerger, A.C. and A.R. Fersht,Structure-function-rescue: the diverse nature of common p53 can...
然而,到目前为止,相比较于wtp53的研究而言,mutp53在癌症中的积累和其GOF的机制尚不完全清楚。 2023年2月7日,美国罗格斯大学Zhaohui Feng和Wenwei Hu教授团队合作在Journal of Clinical Investigation杂志在线发表题为The ubiquitin ligase TRIM21 ...
靶向mutp53 GOF 尽管大多数基于p53的药物开发都是为了恢复癌细胞中野生型p53的活性,但也有人试图通过靶向mutp53快速降解来消除mutp53-GOF(gain-of-function)活性。鉴于HSP90热休克蛋白可以减弱mutp53的降解,研究表明,长时间抑制HSP90可以提高携带mutp53表达肿瘤小鼠的存活率。 03 基于p53的肿瘤免疫治疗 近年来,癌...
p53基因的突变是癌症发生、发展、治疗耐药性和预后不良的重要驱动力。 近日,以色列威茨曼科学研究所的 Moshe Oren 等人在 Nature 系列综述期刊 Nature Reviews Drug Discovery 上发表了题为:Drugging p53 in cancer: one protein, many targets 的综述论文。 这篇综述重新评估了科学界针对p53功能失调性癌症所做的努力,...
2023年2月7日,美国罗格斯大学Zhaohui Feng和Wenwei Hu教授团队合作在Journal of Clinical Investigation杂志在线发表题为The ubiquitin ligase TRIM21 regulates mutant p53 accumulation and gain-of-function in cancer的研究论文。该研究发现,TRIM21是mutp53的关键E3泛素连接酶。TRIM21与mutp53特异性结合,从而导致mutp53...
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。
Zhao X, et al. PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivoJ. Cell Cycle, 2011, 10(2): 301-307.38. Wiman K G. Restoration of WildType p53 Function in Human Tumors: Strategies for Efficient Cancer TherapyJ....
Mutp53 has gain-of-function that plays a key role in promoting malignant phenotype of cancer, and what is the mechanism of its generation of gain-of-function phenotype? Can mutp53 be used as prognostic marker for tumors to make more accurate diagnosis, and monitor the response to treatment ...
Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth TP53 (which encodes p53 protein) is the most frequently mutated gene among all human cancers. Prevalent p53 missense mutations abrogate its tumour suppressive function and lead to a ‘gain-of-function’ (GOF) that prom...
Lu X;Liu DP;Xu Y.The gain of function of p53 cancer mutant in promoting mammary tumorigenesis.Oncogene.2013.2900-2906Lu X, Liu DP, Xu Y (2013) The gain of function of p53 cancer mutant in promoting mammary tumorigenesis. Oncogene 32: 2900 - 2906...