%0 Journal Article
%A Szalóki, Nikoletta
%A Krieger, Jan Wolfgang
%A Komáromi, István
%A Tóth, Katalin
%A Vámosi, György
%T Evidence for Homodimerization of the c-Fos Transcription Factor in Live Cells Revealed by Fluorescence Microscopy and Computer Modeling.
%J Molecular and cellular biology
%V 35
%N 21
%@ 1098-5549
%C Washington, DC
%I Soc.
%M DKFZ-2017-03617
%P 3785 - 3798
%D 2015
%X The c-Fos and c-Jun transcription factors, members of the activator protein 1 (AP-1) complex, form heterodimers and bind to DNA via a basic leucine zipper and regulate the cell cycle, apoptosis, differentiation, etc. Purified c-Jun leucine zipper fragments could also form stable homodimers, whereas c-Fos leucine zipper homodimers were found to be much less stable in earlier in vitro studies. The importance of c-Fos overexpression in tumors and the controversy in the literature concerning c-Fos homodimerization prompted us to investigate Fos homodimerization. Förster resonance energy transfer (FRET) and molecular brightness analysis of fluorescence correlation spectroscopy data from live HeLa cells transfected with fluorescent-protein-tagged c-Fos indicated that c-Fos formed homodimers. We developed a method to determine the absolute concentrations of transfected and endogenous c-Fos and c-Jun, which allowed us to determine dissociation constants of c-Fos homodimers (Kd = 6.7 ± 1.7 μM) and c-Fos-c-Jun heterodimers (on the order of 10 to 100 nM) from FRET titrations. Imaging fluorescence cross-correlation spectroscopy (SPIM-FCCS) and molecular dynamics modeling confirmed that c-Fos homodimers were stably associated and could bind to the chromatin. Our results establish c-Fos homodimers as a novel form of the AP-1 complex that may be an autonomous transcription factor in c-Fos-overexpressing tissues and could contribute to tumor development.
%K Chromatin (NLM Chemicals)
%K Proto-Oncogene Proteins c-fos (NLM Chemicals)
%K Proto-Oncogene Proteins c-jun (NLM Chemicals)
%K Transcription Factor AP-1 (NLM Chemicals)
%K DNA (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26303532
%2 pmc:PMC4589601
%R 10.1128/MCB.00346-15
%U https://inrepo02.dkfz.de/record/127594