dc.contributor.advisor | Wilson, George S. | |
dc.contributor.advisor | Schoeneich, Christian | |
dc.contributor.author | Hewawasam, Geetha S. | |
dc.date.accessioned | 2008-09-08T01:08:15Z | |
dc.date.available | 2008-09-08T01:08:15Z | |
dc.date.issued | 2008-07-29 | |
dc.date.submitted | 2008 | |
dc.identifier.other | http://dissertations.umi.com/ku:2490 | |
dc.identifier.uri | http://hdl.handle.net/1808/4135 | |
dc.description.abstract | Bcl-2 regulates apoptosis by controlling luminal Ca2+ concentration of endoplasmic reticulum (ER). Dremina et al. reported that Bcl-2 interacts with SERCA, the Ca2+ pump in SR/ER membrane, causing inactivation and translocation. This work reports the characteristics of the SERCA/Bcl-2 interactions using wild type and three mutants, G145E, S24C/C158S and S205C/C158S, of the truncated protein, Bcl-2Δ21. Protein cross-linking, Ca2+-ATPase activity assay, Sucrose Density Gradient fractionation, immunoprecipitation and the fusion protein binding assay are the approaches used. Results reveal that the two proteins can interact with both 1:1 and 2:1 (Bcl-2Δ21: SERCA) molar ratios. The hydrophobic groove of Bcl-2Δ21 is involved in the interactions. The BH1 domain of Bcl-2Δ21 interacts with the ATP binding domain of SERCA. The G145E mutant is a loss-of-function whereas the two Cys-mutants are gain-of-function on SERCA inactivation and translocation. Therefore the conserved residue G145 is a critical hot spot for the Bcl-2Δ21-mediated inactivation and translocation of SERCA. | |
dc.format.extent | 169 pages | |
dc.language.iso | EN | |
dc.publisher | University of Kansas | |
dc.rights | This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author. | |
dc.subject | Analytical chemistry | |
dc.subject | Bcl-2 | |
dc.subject | Serca | |
dc.subject | Apoptosis | |
dc.subject | Er | |
dc.subject | Photo cross-linking | |
dc.subject | Protein interactions | |
dc.title | Studies on interactions of Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA) with anti apoptotic protein Bcl-2. | |
dc.type | Dissertation | |
dc.contributor.cmtemember | Givens, Richard S. | |
dc.contributor.cmtemember | Dunn, Robert C. | |
dc.contributor.cmtemember | Desaire, Heather | |
dc.thesis.degreeDiscipline | Chemistry | |
dc.thesis.degreeLevel | PH.D. | |
kusw.oastatus | na | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |