Accumulation of Fra-1 in ras-Transformed Cells Depends on Both Transcriptional Autoregulation and MEK-Dependent Posttranslational Stabilization

• DOI: 10.1128/mcb.23.12.4401-4415.2003
• Publication Date: 2003-05-28T20:41:15Z
• Authors: Laura Casalino; Dario De Cesare; Pasquale Verde
• Keywords: Post-translational regulation; Transcription

The AP-1 transcription factor plays an essential role in cell proliferation and tumorigenesis. It was previously shown that the fra-1 gene product is upregulated by various oncogenes involved vitro vivo transformation of thyroid cells. Here we show ras oncogene-dependent accumulation Fra-1 mediated a positive feedback mechanism which requires both transcriptional autoregulation posttranslational stabilization protein. activation involves cooperation between Raf-dependent Raf-independent pathways site within first intron, becomes stably occupied transcriptionally active Fra-1-containing complex ras-transformed results drastic increase half-life cells totally dependent on activity MEK/ERK phosphorylation pathway. analysis transactivation potential shows protein able to stimulate heterologous promoter ras-dependent manner, but transactivating recruitment heterodimeric partner. These data alteration multiple regulatory mechanisms required for constitutive as nuclear target transformation.