Redox regulation of Ran GTPase.
Ran, a small Ras-like GTP-binding nuclear protein, plays a key role in modulation of various cellular signaling events including the cell cycle. This study shows that a cellular redox agent (nitrogen dioxide) facilitates Ran guanine nucleotide dissociation, and identifies a unique Ran redox architecture involved in that process. Sequence analysis suggests that Dexras1 and Rhes GTPases also possess the Ran redox architecture. As Ran releases an intact nucleotide, the redox regulation mechanism of Ran is likely to differ from the radical-based guanine nucleotide modification mechanism suggested for Ras and Rho GTPases. These results provide a mechanistic reason for the previously observed oxidative stress-induced perturbation of the Ran-mediated nuclear import, and suggest that oxidative stress could be a factor in the regulation of cell signal transduction pathways associated with Ran.
Heo
Jongyun
J
Department of Chemistry and Biochemistry, The University of Texas at Arlington,700 Planetarium Place, Arlington, TX 76019, USA. jheo@uta.edu
D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein; D003545:Cysteine; D009585:Nitrogen Dioxide