Phosphorylation of RCC1 in mitosis is essential for producing a high RanGTP concentration on chromosomes and for spindle assembly in mammalian cells
AUTOR(ES)
Li, Hoi-Yeung
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Spindle assembly is subject to the regulatory controls of both the cell-cycle machinery and the Ran-signaling pathway. An important question is how the two regulatory pathways communicate with each other to achieve coordinated regulation in mitosis. We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of human RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. Moreover, phosphorylation of the NLS of RCC1 is required to prevent the binding of importin α and β to RCC1, thereby allowing RCC1 to couple RanGTP production to chromosome binding. These findings reveal that the cell-cycle machinery directly regulates the Ran-signaling pathway by placing a high RanGTP concentration on the mitotic chromosome in mammalian cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=374234Documentos Relacionados
- The Balance of RanBP1 and RCC1 Is Critical for Nuclear Assembly and Nuclear Transport
- Identification of different roles for RanGDP and RanGTP in nuclear protein import.
- Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1.
- RCC1, a regulator of mitosis, is essential for DNA replication.
- The Dynamic Association of RCC1 with Chromatin Is Modulated by Ran-dependent Nuclear Transport