Histone acetyltransferases and histone deacetylases (HDACs) maintain dynamic acetylation and deacetylation of histories and other proteins in vivo, and are actively involved in the control of gene transcription and other nuclear processes. One mechanism by which functions of these enzymes are regulated operates through differential intracellular compartmentalization. HDAC4, -5, -7 and -9, the four members of class IIa, shuttle between the nucleus and the cytoplasm in a manner dependent on specific phosphorylation stimulated by several known kinases, and these deacetylases possess intrinsic nuclear import and export signals for dynamic nucleocytoplasmic trafficking. The ability to change their intracellular localization implies that class IIa HDACs have some potential functions in different subcellular compartments. To gain additional insights into this, I first focused on studying the function and regulation of HDAC4. As a result, I identified protein kinase D3 as a novel kinase for HDAC4 and found that this kinase physically interacts with HDAC4 and stimulates its nuclear export. Then I tried to purify protein complexes of RFXANK and ANKRA2, two homologous ankyrin-repeat proteins that are known to associate with HDCA4, using the tandem affinity purification (TAP) strategy. The results that I have obtained reveal a novel mechanism for regulating the nuclear export of HDAC4 and suggest that its cytoplasmic localization may also be indicative of potential cytoplasmic functions rather than just for simple sequestration from its nuclear targets.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.98750 |
| Date | January 2006 |
| Creators | Li, Cathy Shije, 1974- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | © Cathy Shije Li, 2006 |
| Relation | alephsysno: 002330663, proquestno: AAIMR24720, Theses scanned by UMI/ProQuest. |
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