Molecular characterization of the protein-protein interaction between HTLV-1 Tax and GSK-3ß
| dc.contributor.author | Wang, Guoliang, author | |
| dc.contributor.author | Nyborg, Jennifer, advisor | |
| dc.contributor.author | Bamburg, James R., committee member | |
| dc.contributor.author | Quackenbush, Sandra L., committee member | |
| dc.contributor.author | Laybourn, Paul J., committee member | |
| dc.date.accessioned | 2022-04-08T19:04:28Z | |
| dc.date.available | 2022-04-08T19:04:28Z | |
| dc.date.issued | 2010 | |
| dc.description | Covers not scanned. | |
| dc.description | Print version deaccessioned 2022. | |
| dc.description.abstract | The human T-cell leukemia virus type 1 (HTLV-1) encodes a viral oncoprotein termed Tax, which plays a major role in transforming HTLV-1- infected cells. Tax is a potent transcriptional activator that stimulates HTLV-1 viral and cellular gene transcription. In addition, Tax disrupts a number of cell signaling pathways involved in cell growth and survival. Glycogen synthase kinase-33 (GSK-33) is a ubiquitously expressed serine/threonine kinase present in all eukaryotic cells, which functions as a critical regulator of a wide range of cell signaling pathways. As GSK-33 is constitutively active in resting cells, it is primarily regulated through inhibition. Ser-9 phosphorylation is inhibitory to the kinase activity of GSK-33. Deregulation of GSK-33 has been linked to many human diseases such as Alzheimer’s disease and cancers. It has been reported in Aida Ulloa’s thesis that Tax inhibits GSK-33 kinase activity toward both primed and non-primed substrates through direct association. To delineate the protein-protein interaction between Tax and GSK-33, we compared the amino acid sequence of Tax with a well-characterized short peptide deriving from the GSK-33 interacting domain (GID) of Axin, and found that Tax contains a notable amino acid sequence homology to Axin GID. The region spanning Tax amino acids 185 - 205 has 24% sequence identity and 19% similarity with Axin GID. We named this region the putative Tax GID. We characterized the putative Tax GID biochemically, and discovered that a longer peptide (Tax aa. 138 - 205) of the putative Tax GID strongly inhibits GSK-3(3 kinase activity in vitro. Bioinformatics computation was used to predict the secondary structure of the Tax GID, which was further used in our docking test to identify a potential binding interface in GSK-3p. This was tested by GST pulldown and Co-IP assays using point and deletion mutants. In addition, the effects of Tax-GSK-3(3 interaction on the downstream (3-catenin and NFAT pathways were characterized by luciferase reporter assays. However, unexpectedly, we observed that Tax expression has little effects on p-catenin and NFAT transcriptional activation. | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier.uri | https://hdl.handle.net/10217/234647 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation | Catalog record number (MMS ID): 991014246929703361 | |
| dc.relation | QR414.5 .W355 2010 | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | HTLV-I (Virus) | |
| dc.subject | Protein-protein interactions | |
| dc.subject | Glycogen synthase kinase-3 | |
| dc.title | Molecular characterization of the protein-protein interaction between HTLV-1 Tax and GSK-3ß | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Biochemistry and Molecular Biology | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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