Importantly, protein activities-based principal-component-analysis multivariate clusters analyzed for independent outcome prediction using Cox proportional-hazards model showed that protein゛ctivity (but not mutation-status) was independently predictive of outcome, demanding a paradigm-shift in patient﹕t...
RAS-protein activation but not mutation status is an outcome predictor and unifying therapeutic target for high-risk acute lymphoblastic leukemia David Koschut, Debleena Ray, Zhenhua Li, Emanuela Giarin, Jürgen Groet, Ivan Alić, Shirley Kow-Yin Kham, Wee Joo Chng, Hany Ariffin,...
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...
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...
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.doi:...
point mutations in Ras prevent the GAP-mediated inhibition of this pathway. The most common oncogenic Ras mutation found in tumors is Gly12 to Asp12 (G12D), which prevents Ras inactivation, possibly by increasing the overall rigidity of the protein. This antibody is predicted to react with H...
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,...
Receptor tyrosine kinases and G protein-coupled receptors activate Ras, which then stimulates the Raf-MEK-MAPK pathway (2-4). GTPase-activating proteins (GAPs) normally facilitate the inactivation of Ras. However, research studies have shown that in 30% of human tumors, point mutations i...
activation [57]. This motif is also present in the human R-RAS2 protein (Figs.1B and3B). Furthermore, in contrast to previous reports using ectopic expression systems that showed subcellular localization of R-RAS2 protein in the plasma membrane, Golgi apparatus, or endoplasmic reticulum [9,...
In parallel with the activation of Ras, the proteins with molecular weights of 52, 56, 62, and 190 kD were tyrosine-phosphorylated and formed a complex with GTPase-activating protein (GAP) for Ras. In addition to the 116-kD GAP (type I GAP), the 100-kD GAP (type II GAP) molecule ...