Background
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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