regardless of mutation status, high-risk leukemic cells could only be killed using RAS‐inhibitor or PTPN11-inhibitor, but not PI3K/JAK‐inhibitors, suggesting a unified treatment target for up to 80% of DS‐ALL. Importantly, protein activities-based principal-component-analysis multivariate clusters ...
In 14 lesions carrying an oncogenic mutation, nonlesional control tissue from the epidermal margin revealed a wild-type sequence, thus proving the somatic character of the mutation. Our results indicate that activation of the RAS-mitogen-activated protein kinase pathway by BRAF and RAS mutations ...
Additionally, RASA1 gene expression has also been described as reduced in hepatocellular carcinoma, leading to aberrant Ras activation. However, loss-of-function mutation of RASA1 is not common in cancer. Instead, another RasGAP, the neurofibromin protein encoded by the NF1 tumor suppressor gene...
There was a more than twofold bias towards Ras-associating protein mutation in GCB (11/24; 46%) versus ABC (3/14; 21%). Further, the gene expression level ofRAS,RAF, and RAS-associating proteins at relapse were higher in GCB-DLBCL compared to ABC-DLBCL (Fig.2B–E, Supplemental Fig.S...
1)功能获得性突变(GOF, gain-of-function mutation) RTK 功能获得性突变导致下游信号转导异常,不受生理信号的调控。比如赋予细胞选择性生长优势的「驱动突变」,有助于识别癌症发生,为靶向治疗提供潜在靶点。突变通常发生在保守残基中,...
This mutation is likely a consequence of vinyl chloride-DNA adduct formation. It leads to the substitution of glycine by aspartic acid in the resulting p21 protein, a consistent amino acid substitution found so far in all types of human cancer exhibiting a codon 13-mutated Ki- ras gene....
activationofmitogenactivatedproteinkinase. JBielChem.1996,271:14560~l4566 l0StokoeD.MacdonaldSG.Cadwal1 且derKet a1.ActivationofR^f 雎n~eault0frecruitment totheplasmam*mhrane.Science.1994?264: 1463～1467 llHallhergB.RayterSI,DownwardInter— actionofRa 旦andRafinjntactmammaliancalh ...
In conclusion, simultaneous K-ras activation and Keap1 deletion caused progressive atrophy of the pancreatic parenchyma in mice. NEW & NOTEWORTHY Aberrant activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system usually promotes carcinogenesis, and we ...
In binding experiments Rhes, as another membrane protein, sodium/iodide symporter (NIS), reduced membrane expression of wt TSHr (wtTSHr). In conclusion, Rhes can interfere with the functional activity of wt and mutated TSHr and with the respective hormone-stimulated cAMP production of FSHr and ...
The importance of mutational activation of the Ha-ras protooncogene in polycyclic aromatic hydrocarbon-induced mouse skin tumors was investigated in a complete carcinogenesis model using repetitive applications of 7,12-dimethylbenz[a]anthracene (DMBA), or in an initiation-promotion model using a single...