Nucleoporins mediate nucleocytoplasmic trafficking in interphase. In mitosis, upon nuclear envelope breakdown, the role and regulation of Nups remain to be elucidated. An important subcomplex of nucleoporins is the Nup107-160 complex, which, in mitosis, is involved in spindle assembly and nuclear pore re-assembly. Here we show that the level of a key constituent of the Nup107-160 complex- Nup96 is cell cycle regulated. We found that the mechanism involved in regulating Nup96 levels in mitosis is proteolysis by the anaphase-promoting complex (APC). Nup96 interacts with the APC, and its proteolysis can be regulated by Cdc20 and Cdh1. Like the Nup107-160 complex, the APC is localized at kinetochores, centrosomes, and spindles. Disruption of Nup96 levels led to an acceleration of prophase to prometaphase transition and, most importantly, resulted in a delay of G1 progression. Thus, regulation of Nup96 proteolysis in mitosis sets the stage for proper G1 progression. Additionally, we have observed differential regulation of members of the Nup107-160 complex during mitosis and have identified interacting partners of Nup96 at the centrosome which reveal a novel role of nucleoporins in regulating microtubule nucleation.
| Identifer | oai:union.ndltd.org:UMIAMI/oai:scholarlyrepository.miami.edu:oa_dissertations-1053 |
| Date | 27 June 2007 |
| Creators | Chakraborty, Papia |
| Publisher | Scholarly Repository |
| Source Sets | University of Miami |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Open Access Dissertations |
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