来自美国罗格斯大学的Zhaohui Feng团队在JCI上发表题为“The ubiquitin ligase TRIM21 regulates mutant p53 accumulation and gain of function in cancer”的研究成果,该研究揭示了 mutp53 在癌症中积累的关键机制,揭示了 TRIM21 的抑癌...
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...
GOF突变p53也被报道可以增强蛋白酶体基因的表达,保护癌细胞免受蛋白毒性应激,赋予癌细胞对蛋白酶体抑制剂的耐药性。 参考文献:Zhang C, Liu J, Xu D, Zhang T, Hu W, Feng Z. Gain-of-function mutant p53 in cancer progression and therapy. J Mol Cell Biol. 2020 Sep 1;12(9):674-687....
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,...
2024年12月4日，复旦大学生物医学研究院/附属肿瘤医院周祥团队与南昌大学第一附属医院熊建萍/邓军团队在Molecular Cell期刊上发表了题为p53 induces circFRMD4A to suppress cancer development through glycolytic reprogramming and cuproptosis的研究论文，首次揭示p53促进肿瘤细胞铜死亡的现象及分子机理，并证实了p53激动...
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[7] Zhou X,Hao Q,Lu H. Mutant p53 in cancer therapy-the barrier or the path[J]. J Mol Cell Biol,2019,11(4):293-305. [8] Liao P,Zeng S X,Zhou X,et al. Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding[J...
Gain of functionCancerHER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of...
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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。