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Title: Mapping of polyomavirus middle T domain that is responsible for AP-1 activation. Author: Oliveira ML, Roberts TM, Druker BJ, Armelin MC. Journal: Oncogene; 1998 Jun 11; 16(23):2975-82. PubMed ID: 9662329. Abstract: Cell transformation by Polyomavirus middle T (MT) oncoprotein involves binding and activation of several cytoplasmic proteins that participate in growth factors-induced mitogenic signal transduction to the nucleus. We have previously reported that the AP-1 transcriptional complex is a target for MT during cell transformation. To analyse the interactions between MT and cellular proteins that are required for constitutive AP-1 activation, we compared wild type and transformation-defective MT mutant cell lines. High AP-1 activity, assessed by gel mobility shift assays, displayed by MT-overexpressing cells, is dependent on MT binding to phosphatidylinositol-3 kinase (P13K). Treatment with wortmannin (a specific P13K inhibitor) leads to decreased AP-1 activity. Supershift and Western blot analysis with specific antisera, indicate that JunB and cJun, but not cFos or FosB are present in the AP-1 complex. The results confirm the AP-1 complex as a downstream MT target and indicate that AP-1 activation may not be sufficient for cell transformation, since two transformation-defective MT mutants (250phe and MT322) display high AP-1 activity.[Abstract] [Full Text] [Related] [New Search]