C-Raf

C-Raf (RAF1) is a serine/threonine protein kinase of the RAF family that functions as a MAP kinase kinase kinase (MAP3K) downstream of RAS GTPases and serves as a central regulator of the RAS-RAF-MEK-ERK signaling cascade.^[1][2] Upon activation by RAS, C-Raf phosphorylates MEK1 and MEK2, which subsequently activate ERK1/2, thereby controlling gene expression programs associated with cell-cycle progression, differentiation, migration, apoptosis regulation, and cellular survival.^[1][2] Mechanistically, C-Raf acts as a key signal transducer that links extracellular growth-factor stimulation to intracellular MAPK signaling and amplifies biological responses through kinase cascade activation.^[1][2] In disease settings, aberrant RAF1 signaling contributes to oncogenic processes, and RAF1-dependent signaling has been implicated in tumor proliferation, survival, and transformation models.^[3] Compared with related RAF isoforms, C-Raf belongs to a three-member kinase family consisting of A-Raf, B-Raf, and C-Raf, but it exhibits distinct regulatory properties mediated by its RAS-binding region, autoinhibitory mechanisms, and protein-protein interaction networks.^[2] Beyond its canonical kinase activity, experimental studies indicate that RAF1 can support cellular proliferation through kinase-independent functions, highlighting additional scaffold-like roles in signaling complexes.^[3] For experimental applications, pharmacological RAF inhibitors and emerging RAF1-targeting degradation strategies are widely used to interrogate RAF-dependent signaling mechanisms and evaluate pathway vulnerabilities in cancer models.^[3]