Transcription activation by the transforming domain of adenovirus E1A is efficiently repressed by the last 44 amino acids of E1A

Abstract

REPRESSION OF THE c-JUN trans-ACTIVATION FUNCTION BY THE ADENOVIRUS TYPE 12 E1A 52R PROTEIN CORRELATES WITH THE INHIBITION OF PHOSPHORYLATION OF THE c-JUN trans-ACTIVATION DOMAIN. D. Brocknu an, G. KrOner, C. Bury and H. Esche. The cellular transcription factor complex AP-1 mediates growth factor signals on the level ofgene expression and is considered to be decisive in cell differentiation, proliferation and transformation. AP-1 consists mainly of proteins encoded by the jun gene family (c-jun, junB, junD) and the fos gene family (c-los, fosB) including thefos-related antigensfral andfra2. The early region 1A (E1A) 52R polypeptide, a protein expressed exclusively by the in vivo oncogenic Adenovims subtype 12 (Adl2), represses the trans-activating activity of AP-1 consisting of c-Jun:c-Jun homodimers. Repression is accompanied by a direct physical interaction of the adenovirus protein with the bZIP domain of c-Jun essential for dimerization and DNA-binding. Interestingly this interaction does not lead to the prevention of the promoter bindung of c-Jun/AP-1. Moreover, the association between c-JUN and the TATA-box binding protein TBP is not disturbed by the 52R polypeptide. Down-regulation of c-Jun activity is rather due to the inhibition of the phosphorylatinn of its acidic trans-activation domain located at the amino terminal end. In vivo phosphorylation of the cJun trans-activation domain by JNK kinases enzymes belonging to the mitogen-activated protein (MAP) kinase group is necessary for the interaction of c-Jun with specific co-factors like CBP and therefore a prerequisite for the activation of specific target genes. Due to these results we propose a model in which the 52R protein represses the trans-activating activity of c-Jun by prevemijag its phosphorylation through a JNK kinase(s). (Supported by the Deutsche Forschungsgemeinschaft through SFB 354/TP3 and the Fonds der Chemischen Industrie.)

DOI: 10.1007/BF02559858

Cite this paper

@article{Sollerbrant2007TranscriptionAB, title={Transcription activation by the transforming domain of adenovirus E1A is efficiently repressed by the last 44 amino acids of E1A}, author={Kerstin Sollerbrant and A. Richnau and Goran Akusj{\"a}rvi and Catharina Svensson}, journal={Journal of Cancer Research and Clinical Oncology}, year={2007}, volume={121}, pages={S26-S26} }