FoxO6 transcriptional activity is regulated by Thr26 and Ser184, independent of nucleo-cytoplasmic shuttling

• DOI: 10.1042/bj20050525
• Publication Date: 2005-10-27T08:30:18Z
• Authors: Lars P. van der H...; Frank M. J. Jacobs; J. Peter H. Burbach; Marco F. M. Hoekman; Marten P. Smidt
• Keywords: Cell Nucleus; Threonine; 0301 basic medicine; Cytoplasm; Transcription, Genetic; Amino Acid Motifs; Forkhead Transcription Factors; Cell Line; Protein Structure, Tertiary; Protein Transport; 03 medical and health sciences; Mutation; Serine; Humans; Phosphorylation

Forkhead members of the ‘O’ class (FoxO) are transcription factors crucial for regulation metabolism, cell cycle, death and survival. FoxO regulated by insulin-mediated activation PI3K (phosphoinositide 3-kinase)–PKB (protein kinase B) signalling. Activation PI3K–PKB signalling results in phosphorylation on three conserved motifs, which essential translocation from nucleus to cytosol. FoxO6, however, remains mostly nuclear due fact that its shuttling ability is dramatically impaired. FoxO1, FoxO3 FoxO4 all contain an N- C-terminal PKB motif a located forkhead domain. FoxO6 lacks motif, cause impairment. Since can be considered constitutively nuclear, we investigated whether it also active factor. Our show transcriptional activity inhibited growth factors, independent shuttling, indicating not active. The site domain (Ser184) DNA binding characteristics N-terminal acted as factor sensor. In summary, Thr26- Ser184-dependent manner,