Ras-related protein Ral-B (RalB) (RalB)

Ras-related protein Ral-B (RalB) is a small GTPase belonging to the Ras superfamily that acts as a critical molecular switch in signal transduction pathways (UniProt P11234). It cycles between an active GTP-bound state and an inactive GDP-bound state, a process regulated by Ral-specific guanine nucleotide exchange factors (RalGEFs) and GTPase-activating proteins (GAPs) (Gentry et al., 2014). RalB is uniquely involved in the regulation of autophagy and exocytosis, where it coordinates the assembly of the exocyst complex to facilitate vesicle transport and cell survival under stress (Bodemann et al., 2011). In human oncology, RalB is often hyperactivated downstream of oncogenic Ras mutations, driving tumor progression, chemoresistance, and metastasis in pancreatic, lung, and colorectal cancers (Yan et al., 2014). Because the active state has proven difficult to target directly, drug discovery efforts have focused on the RalB-GDP conformation, utilizing allosteric inhibitors like RBC8 and BQU57 that bind to a surface cavity available in the inactive state to prevent GEF-mediated activation (Yan et al., 2014). These small molecules have demonstrated efficacy in preclinical models by inhibiting Ral-dependent signaling and reducing tumor growth, marking RalB as a high-priority therapeutic target in Ras-driven malignancies.

Other names

RALBRas-related protein Ral-BGTP-binding protein RALB

Allosteric inhibition of RalB activation by binding to the GDP-bound state and preventing effector interaction.