The Ras family small GTPase Ran is involved in nuclear envelope formation, assembly of the mitotic spindle, and nuclear transport. Like other small GTPases, Ran is active in its GTP-bound form and inactive in its GDP-bound form. Nuclear RanGTP concentration is maintained through nuclear localization of guanine nucleotide exchange factor activity, which catalyzes the exchange of bound GDP for GTP. Regulator of chromatin condensation 1 is the only known RanGEF. RCC1 is dynamically chromatin-bound throughout the cell cycle, and this localization is required for mitosis to proceed normally. Appropriate association of RCC1 with chromatin is regulated through amino-terminal phosphorylation and methylation. RCC1 regulation of RanGTP levels in response to histone modifications regulates nuclear import during apoptosis. In mitosis RCC1 is phosphorylated at Ser11, possibly by cyclin B/cdc2. This phosphorylation may play a role in RCC1 interaction with chromatin and RCC1 RanGEF activity.
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