The functional integrity of the nuclear pore complex (NPC) is achieved through the fastening to the pore membrane (POM) proteins. This interlocked zipper of proteins is important to maintain nuclear transport and allow proper progression through the cell cycle. NPCs are disassembled into nucleoporins (Nup) subcomplexes during entry into open mitosis in higher eukaryotic cells. POM proteins have been shown to affect cell cycle progression and to be involved in several disease states such as leukemia, heart disease and types of progeria. We hypothesize that Nup/POM interfaces are regulated by mitotic kinases at disassembly leading to their release and mitotic localization. To study this we propose: The determination of key phosphorylation interface targets and pairing them as substrates for kinases involved in disassembly and distribution of the NPC. We will identify and test these regulated areas including constraint-based modeling from our phosphorylation/interaction mapping. This work will be the key prerequisite to understand NPC regulation and distribution throughout the cell cycle.
Abnormal growth and development can lead to many disease states. Life-threatening disorders such as Leukemia, heart disease and severe aging are a result of alternated proteins. These conditions collectively have a high impact on health, affecting tens of thousands of people in the United States alone. This project is designed to identify modified molecular targets within the nuclear pore complex and pore membrane that can lead to the detection and treatments for patients.
| Shah, Munish B; Chang, Wei; Zhou, Gan et al. (2018) Novel spiral structured nerve guidance conduits with multichannels and inner longitudinally aligned nanofibers for peripheral nerve regeneration. J Biomed Mater Res B Appl Biomater : |
