2021年3月19日 · We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in...

大规模基因组测序研究揭示了PDAC发生与发展的驱动因子，主要包括癌基因KRAS和抑癌基因TP53的突变。 根据TCGA项目数据显示，KRAS 错义突变 可发生在超过90%的PDAC病人中，而TP53错义突变及截断突变亦可发生在高达70%的案例中【1】；这些驱动突变事件（driver mutation）在PDAC中的高频率发生也得到了近期发表的癌症全基因组测序项目的支持【2】。 其中，KRAS作为Ras小GTP酶家族中的主要基因成员，其携带的激活型突变主要通过增强结 …

TP53 is a gene that encodes for the p53 tumor suppressor protein, commonly referred to as the “Guardian of the Genome” [1]. Its main biological function appears to involve the protection of the DNA integrity of the cell. TP53 plays additional roles …

Mutant p53 increases expression of splicing regulator hnRNPK to promote inclusion of cytosine-rich exons within GTPase-activating proteins (GAPs), negative regulators of RAS family members. Mutant p53-enforced GAP isoforms lose cell membrane association, leading to …

2019年1月30日 · Wild-type p53 expression in RAS mutant cells enhances HIF-1α turnover in ovarian and lung cancer cells. Autophagy and anti-apoptotic processes can be promoted by the overexpression and cytoplasmic translocation of HDAC4 and HIF1-α.

2022年5月10日 · This study describes the functional kinomic landscape of Ras/p53 mutant chemically-induced squamous cell carcinoma in both the baseline unperturbed state and following DNA damage and nominates ...

研究人员利用这种双特异性抗体成功靶向了p53和RAS，在体外和动物肿瘤模型中进行的测试也证明了这种疗法抑制肿瘤生长的潜力。 Bert Vogelstein教授是癌症基因组学领域的先驱。 1989年，他的团队发现 p53基因 是癌症中最常见的突变基因，而且揭示了癌症是由特定的癌基因和抑癌基因的基因改变逐渐累积所导致的。 在研究过程中，研究人员注意到，RAS和p53突变蛋白虽位于胞内，但会在细胞内水解产生肽，这些肽段可在与人类白细胞抗原（HLA）蛋白形成复合 …

2019年1月30日 · The interplay between p53 and RAS signaling regulates cancer chemoresistance, but the detailed mechanism is unclear. In this study, we investigated the interactive effects of p53 and RAS on ovarian cancer cisplatin resistance to explore the potential therapeutic targets.

近日，在《Science》和《Science Immunology》上发布的两项最新研究中，由约翰霍普金斯大学领衔的研究团队成功研发出靶向RAS和p53突变体的双特异性抗体疗法。能够识别携带RAS基因突变或者 TP53基因突变 的肿瘤细胞，并激发T细胞消灭携带这些突变的肿瘤细胞。与 ...

2012年7月1日 · From this study we suggest that different mutant p53 categories cooperate with H-Ras in different ways to induce a unique expression pattern of a cancer-related gene signature (CGS). The DNA-contact p53 mutants (p53(R248Q) and p53(R273H)) exhibited the highest level of CGS expression by cooperating with NFκB.