Human T-cell Leukemia Virus Type I Tax Masks c-Myc Function through a cAMP-dependent Pathway (∗)

摘要: Human T-cell leukemia virus type I Tax is a pleiotropic gene regulator that functions through CREB/ATF- and NF-κB-mediated pathways. In most contexts, potent activator. Here, we describe an unexpected finding of Myc repression by Tax. cells overexpress human Tax, the detection c-Myc protein in nucleus monoclonal antibody was masked. prevented immunological visualization epitope contained within amino acids 45-104, resulting interference with function transcription anchorage-independent cell growth. did not affect steady-state levels since other antibodies unperturbed. Four observations suggest this Tax-Myc interaction mediated CREB/ATF signal transduction. 1) point mutants, selectively defective for activation but NF-κB, failed to mask c-Myc; 2) masking abolished when Tax-expressing were treated kinase inhibitor H-9; 3) Tax-specific shielding absent (B1R) are genetically cAMP signaling; 4) forskolin treatment mimicked epitope. Considered collectively, these findings regulation at level localized conformation.