Fig. 1
From: Targeting CRAF kinase in anti-cancer therapy: progress and opportunities
Structure and molecular alteration of CRAF in TCGA patient cohorts. a Three conserved regions (CR1–CR3) are indispensable in activating CRAF by RAS-GTP. CR1, located at the N-terminus of CRAF, is comprised of the Ras-binding domain (RBD) and cysteine-rich domain (CRD). The CRD maintains the auto-inhibited state of CRAF through interacting with 14-3-3 and the C-terminal kinase domain. The CR2 region consists of a serine-threonine-rich segment and recognizes a series of regulators, including 14-3-3, Hsp90, CDC37, and prohibitin. The auto-inhibited CRAF monomer requires a 14-3-3 dimer to bind to phosphorylated Ser 259 in the CR2 region. The CR3 region is comprised of the protein kinase domain and a short C-terminal tail harboring the second binding site for 14-3-3 proteins. Point mutations are depicted as small colored dots in the graph. Blue dots represent point mutations in CRAF that result in inhibitory effects, while red dots represent point mutations that lead to activating effects. b The alteration of CRAF based on TCGA Pan-cancer Atlas studies as visualized on the UniProt data platform. In the figure, the "+" symbols below each tumor type indicate that the bar graph analysis incorporates "structural variants", "mutations", and "Copy Number Alterations (CNA)" for that specific tumor type. BLCA, Bladder Urothelial Carcinoma; SKCM, Skin Cutaneous Melanoma; DLBC, Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; UCEC, Uterine Corpus Endometrial Carcinoma; STAD, Stomach adenocarcinoma; ESAD, Esophageal adenocarcinoma; SARC, Sarcoma; KIRC, Kidney renal clear cell carcinoma; COAD, Colon adenocarcinoma; THCA, Thyroid carcinoma; BRCA, Breast invasive carcinoma; LUAD, Lung adenocarcinoma; LIHC, Liver hepatocellular carcinoma; KIRP, Kidney renal papillary cell carcinoma; OV, Ovarian serous cystadenocarcinoma; CESC, Cervical squamous cell carcinoma and endocervical adenocarcinoma; LGG, Lower Grade Glioma; LUSC, Lung squamous cell carcinoma; THYM, Thymoma; PRAD, Prostate adenocarcinoma; GBM, Glioblastoma multiforme; TGCT, Testicular Germ Cell Tumor; HNSC, Head and Neck squamous cell carcinoma; PCPG, Pheochromocytoma and Paraganglioma