Sequestration of the Transcription Factor STAT3 by the Molecular Chaperone CCT: A Potential Mechanism for Modulation of STAT3 Phosphorylation

• The molecular chaperone CCT has functions in addition to protein folding. oncogenic transcription factor STAT3 binds oligomer. is not an obligate folding substrate of CCT. Reduction levels leads enhanced phosphorylation MCF7 cells. Sequestration by may provide a means regulate phosphorylation. Chaperonin Containing Tailless complex polypeptide 1 (CCT) essential required for the abundant proteins actin and tubulin. oligomer also folds range other participates non-folding activities such as providing assembly support complexes von Hippel Lindau tumor suppressor elongins. Here we show that oligomer, but does display early binding upon translation rabbit reticulocyte lysate typical substrate. Consistent with this, depletion each subunits siRNA targeting indicates loss suppress activation steps stimulation IL-6: phosphorylation, dimerisation nuclear translocation. Furthermore, transcriptional activity negatively affected reduction levels. Instead, cells enhancement at Tyr705, implicating role sequestration non-phosphorylated STAT3. Thus, dynamic state abundance modulate