Figure 2.
Ran/Crm1 functions as a loading dock to coordinate cell cycle checkpoints and centrosome duplication. The centrosome duplication cycle is shown through the various stages of the cell cycle. The Ran/Crm1 network functions as a loading dock to spatially and temporally coordinate NES-containing factors that ensure the fidelity of the centrosome duplication process. The Ran/Crm1 complex interacts with various NES-containing proteins, such as NPM, p53, BRCAs, etc., in a cell cycle dependent manner to inhibit centriole splitting. At the G1/S transition of a normal cell, such a process may be inactivated by phosphorylation of the substrates, such as NPM, thereby preventing their bindings to Ran/Crm1. Disruption of this coordination may lead to genomic instability and carcinogenesis.