| Publication Type |
dissertation |
| School or College |
School of Medicine |
| Department |
Pathology |
| Author |
Gunther, Cathy Veronica |
| Title |
Regulation of Moloney murine retrovirus transcription by the ETS gene family |
| Date |
1994-03 |
| Description |
The retroviral long terminal repeat (LTR) can serve as a probe for identifying eukaryotic transcription factors that function as determinants of viral gene expression and tumor formation. The ets-1 cDNA was cloned based on its ability to express a protein that binds to a transcriptional activator sequence in the Moloney murine sarcoma virus (MoMUSV) promoter. Two additional binding sites for Ets-1 were identified in the Moloney virus enhancer. Mutations in these sites reduced the transcriptional efficiency of the LTR in cultured T-cells and attenuated enhancer-mediated responsiveness to phorbol esters, which stimulate transcription via protein kinase C signaling pathways. Ets-1 is a member of a gene family that shares sequences similarity within an 85 amino acid region, termed the ETS domain. The unique structure of the ETS DNA-binding domain distinguished the ets family as a novel class of transcription factors. The positive correlation between Ets-1 binding sites and Moloney transcriptional regulatory sequences on the LTR suggested a possible function of ETS domain proteins as regulatory of Molonely virus transcription. To determine which ETS domain proteins were the most likely candidates for this regulation, the transcriptional activity of the Mo-MuLV LTR is a cultured T-cell line was measured and correlated with the expression and binding patterns of known ets genes in mice. Murine T-cells express at least five different ets genes; the binding characteristics of these ETS domain proteins are very similar in vitro. To distinguish between these potential regulatory activities, nuclear extracts made from t-cell were analyzed for enhancer-binding activity in vitro. UV crosslinking identified two predominant binding activities in crude extracts: a 55 kDa species and a 100 kDa species. Based on its reactivity with antibody probes, was identified as the ETS domain protein GABP?. p100 was not reactive with available antibody probed; however, in vitro contract mapping experiments demonstrated that this activity bound to DNA with the same pattern, or signature," as three other ETS domain proteins, By these criteria, p100 was also classified as an ETS domain protein. The presence of multiple ETS domain proteins in T-cells that bind to the enhancer in vitro suggest the Mo-MuLV might utilize the regulatory potential of multiple members of the ETS domain protein family in vivo in order to optimize its expression. |
| Type |
Text |
| Publisher |
University of Utah |
| Subject |
Viral Genetics; Retoviruses; Murine Saarcoma Viruses |
| Subject MESH |
Genetics; Elastin |
| Dissertation Institution |
University of Utah |
| Dissertation Name |
PharmD |
| Language |
eng |
| Relation is Version of |
Digital reproduction of "Regulation of Moloney murine retrovirus transcription by the ETS gene family." Spencer S. Eccles Health Sciences Library. Print version of "Regulation of Moloney murine retrovirus transcription by the ETS gene family." available at J. Willard Marriott Library Special Collection. QR6.5 1994 .G85. |
| Rights Management |
© Cathy Veronica Gunther. |
| Format Medium |
application/pdf |
| Format Extent |
6,250,932 bytes |
| Identifier |
undthes,4851 |
| Source |
Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available). |
| Funding/Fellowship |
Predoctoral fellowship from the NIH Cancer Training Grant 5-T32 CA09602, and from a March of Dimes Basic Research Grant 1-0138 awared to B.J. Graves. |
| Master File Extent |
6,250,950 bytes |
| ARK |
ark:/87278/s6dr2xcp |
| Setname |
ir_etd |
| ID |
191517 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6dr2xcp |
