GTP-binding nuclear protein Ran (RAN) (RAN)

GTP-binding nuclear protein Ran (RAN), a member of the Ras superfamily of small GTPases, acts as a critical molecular switch that regulates essential cellular processes including nucleocytoplasmic transport and mitosis [4, 13]. It cycles between an active GTP-bound state and an inactive GDP-bound state, a process controlled by regulators like RCC1 in the nucleus and RanGAP1 in the cytoplasm [1, 14]. During interphase, the Ran-GTP gradient across the nuclear envelope drives the transport of proteins and RNA through the nuclear pore complex [12, 15]. In mitosis, Ran is indispensable for spindle assembly, chromosome segregation, and nuclear envelope reassembly [2, 16]. Ran is frequently overexpressed in various malignancies, such as ovarian, breast, and pancreatic cancers, where it promotes tumor progression, metastasis, and resistance to chemotherapy [8, 9, 14]. Experimental inhibitors like the small molecule M36 and specific inhibitory peptides are being developed to target Ran by locking it in its inactive state, thereby inducing apoptosis in cancer cells while potentially sparing normal tissues [11, 13]. This targeting strategy aims to disrupt the vital transport and mitotic processes that transformed cells rely on for rapid proliferation and survival.

Other names

Ras-related nuclear proteinARA24TC4GSP1GSP2Small GTP-binding protein Ran

Inhibition of the Ran GTPase cycle by locking the protein in its inactive GDP-bound state, thereby disrupting nucleocytoplasmic transport and mitotic spindle assembly [11, 13].