Oncogenic Subtypes Research Articles

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 Activation Domain

The early region 1A 52R polypeptide, a protein expressed exclusively by the in vivo oncogenic adenovirus subtype 12, represses the trans-activating function of the cellular transcription factor complex AP-1 consisting of c-Jun-c-Jun homodimers. In this report we demonstrate that the repression in vivo correlates with a direct physical interaction of the adenovirus protein with c-Jun in vitro. Interestingly, the 52R protein binds to the bZIP domain of c-Jun essential for dimerization and DNA binding but not to the c-Jun activation domain. This interaction does not prevent the promoter binding of c-Jun/AP-1. Moreover, the physical association between c-Jun and the TATA box-binding protein TBP is not disturbed by the 52R polypeptide. In fact, we show evidence that down-regulation of c-Jun activity by the adenoviral protein is due to the inhibition of phosphorylation of the c-Jun trans-activation domain. In vivo phosphorylation of the c-Jun activation domain is necessary for the interaction of c-Jun with specific cofactors such as CBP and therefore a prerequisite for the activation of target genes. Due to these results we propose a model in which the 52R protein represses the trans-activating function of c-Jun by preventing its phosphorylation through a specific kinase necessary for the activation of the cellular transcription factor.

Adenovirus Type 12 Early Region 1A Expresses a 52R Protein Repressing the trans-Activating Activity of Transcription Factor c-Jun/AP-1

Oncoproteins of the early transcription unit 1A (E1A) of adenoviruses (Ad) are known to modulate the expression of all viral and of a variety of cellular genes. In this communication we present data demonstrating for the first time an activity associated with a protein (the 52R protein) expressed exclusively from E1A of the highly oncogenic subtype Ad 12. The 52 R protein, which does not contain any of the conserved regions (CR1-CR3) necessary for the trans -regulatory functions of the larger E1A proteins (266R, 235R), represses the trans-activating activity of the transcription factor cJun/AP-1. The repression of c-Jun/AP-1 activity is neither due to a down-regulation of the c-jun transcription rate nor due to an inhibition of binding of the transcription factor complex to its target sequence, at least under the conditions of in vitro band shift assays. As the 52R protein is most probably not associated with DNA-bound c-Jun/AP-1, we suppose that it represses c-Jun activity either by a squelching mechanism sequestering a cofactor, which is an essential link between c-Jun/AP-1 and the components of the basal transcriptional machinery or by modifying post-translational modifications necessary for the trans-activation function of c-Jun.

Sunlight, HPV, and the Risk of Skin Cancer in Renal Transplant Patients

Nonmelanoma skin cancer is common in renal transplant patients. The importance of childhood sun exposure or specific human papillomavirus (HPV) types in the development of skin cancers in these patients is not known. Does sun exposure at an early age have a greater influence on the development of skin cancers than recent exposure? Do specific HPV subtypes correlate with benign lesions, while oncogenic HPV subtypes correlate with skin cancers? Two recent retrospective studies attempted to answer these …

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