The Biological Consequences and Molecular Basis of Jun-Mediated Autorepression in Avian Fibroblasts

Kilbey, Anna C (1995) The Biological Consequences and Molecular Basis of Jun-Mediated Autorepression in Avian Fibroblasts. PhD thesis, University of Glasgow.

Abstract

c-Jun expression is down-regulated in v-Jun- and c-Jun-transformed chicken embryo fibroblasts. The down-regulation is a specific consequence of high Jun expression suggesting that c-jun, like several other immediate early genes, is subject to negative autoregulation. The work in this thesis has attempted to define the consequences of and the molecular basis for Jun-mediated autorepression in vivo. c-Jun is the sole or predominant Jun family protein expressed in primary CEFs. Repression of endogenous p39 c-Jun in ASV17-transformed cultures results in the replacement of c-Jun-containing AP-1/TRE binding complexes with v-Jun-containing alternatives. The absence of auxiliary Jun family proteins facilitates the displacement and may contribute to the unique transforming activites of v-Jun (and c-Jun) in avian cells. v-Jun-mediated auto-repression is primarily directed at the level of transcription and correlates with specific changes in occupancy at the proximal junTRE and adjacent junRSRE binding sites in the c-jun promoter. In normal asynchronous cultures specific binding factors compete for the adjacent junTRE and junRSRE regulatory elements. In ASV17-transformed cells the junTRE is exclusively occupied by v-Jun-containing complexes and endogenous c-jun expression is down-regulated. The absence of junRSRE occupancy in ASV17-transformed cells is associated with high levels of the v-Jun oncoprotein which physically disrupt or inhibit the binding activity of junRSRE-specific complexes. Mutually exclusive binding at the junTRE and junRSRE or a Jun-dependent sequestration of specific accessory factors have been proposed to direct the single pattern of occupancy in ASV17-transformed cells and to, thereby, contribute to the down-regulation of endogenous c-jun expression.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Dave Gillespie
• Keywords: Molecular biology, Developmental biology
• Date of Award: 1995
• Depositing User: Enlighten Team
• Unique ID: glathesis:1995-74817
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 16:00
• Last Modified: 27 Sep 2019 16:00
• URI: https://theses.gla.ac.uk/id/eprint/74817