Disease relevance of Ran

• At early embryonic stages of mouse development we found persistent Ran expression in proliferating neural tissue, neural crest derived dorsal root ganglions and sensory pits [1].
• Differential expression of Ran GTPase during HMBA-induced differentiation in murine erythroleukemia cells [2].

High impact information on Ran

• RanGDP binding to the NPC is not mediated by the Ran binding sites of importin-beta, suggesting that translocation is not driven from these sites [3].
• Translocation of the resulting import ligand complex through the nuclear pore complex (NPC) requires Ran and is terminated at the nucleoplasmic side by its disassembly [3].
• Therefore, import might involve nucleotide exchange and GTP hydrolysis on NPC-bound Ran [3].
• We report that Tax directly binds Ran and Ran-binding protein-1, locates to centrosomes/spindle poles, and causes supernumerary centrosomes [4].
• The X-linked RP3 locus codes for retinitis pigmentosa GTPase regulator (RPGR), a protein of unknown function with sequence homology to the guanine nucleotide exchange factor for Ran GTPase [5].

Biological context of Ran

• Anti-Ran antibody microinjection decreased the germinal vesicle breakdown and the first polar body extrusion, and distorted spindle organization and chromosome alignment [6].
• The small GTPase Ran functions in several critical processes in eukaryotic cells including nuclear transport, nuclear envelope formation, and spindle formation [7].
• The small GTPase Ran controls numerous cellular processes of the mitotic cell cycle [6].
• Functions of the Spa-1 protein and its regulation are discussed in the context of its possible interaction with the Ran/RCC-1 system, which is involved in the coordinated nuclear functions, including cell division [8].
• The Ran GTPase plays a central function in control of nucleo-cytoplasmic transport in interphase [9].

Anatomical context of Ran

• Ran/M2 is testis specific, whereas the Ran/M1 isoform is also expressed in somatic tissues [10].
• Cell cycle-dependent localization and possible roles of the small GTPase Ran in mouse oocyte maturation, fertilization and early cleavage [6].
• The Ran GTPase network controls several cellular processes, including nucleocytoplasmic transport and cell cycle progression, and has recently also been shown to regulate microtubule nucleation and spindle assembly in Xenopus oocyte extracts [11].
• The cell line tsBN2 contains a temperature-sensitive point mutation in the RCC1 gene, which encodes a guanine nucleotide exchange factor of Ran [12].
• On the other hand, a high level of overexpression of Ran in both macrophages and B cells down-regulates LPS signal transduction [13].

Associations of Ran with chemical compounds

• The involvement of Ran GTPase in lipopolysaccharide endotoxin-induced responses [13].
• The Ran GTPase Mediates Chromatin Signaling to Control Cortical Polarity during Polar Body Extrusion in Mouse Oocytes [14].
• To identify genes involved in the commitment of MEL cells to differentiate, we screened a cDNA library constructed from HMBA-induced cells by differential hybridization and isolated GTPase Ran as a down-regulated gene [2].

Regulatory relationships of Ran

• At the nonpermissive temperature, importin-beta was exported from the nucleus of these cells, even when RanGAP1, a GTPase-activating protein for Ran, was co-injected [12].

Other interactions of Ran

• The results indicate that the novel nuclear protein Spa-1, with a potentially active Ran GAP domain, severely hampers the mitogen-induced cell cycle progression when abnormally and/or prematurely expressed [8].
• Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors [15].
• Consistently, a mutant importin-beta deficient in Ran binding can deliver its cargo up to the nucleoplasmic side of the NPC [3].

Analytical, diagnostic and therapeutic context of Ran

• Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase-activating domain that affects cell cycle progression [8].

References