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000127594 037__ $$aDKFZ-2017-03617
000127594 041__ $$aeng
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000127594 1001_ $$aSzalóki, Nikoletta$$b0
000127594 245__ $$aEvidence for Homodimerization of the c-Fos Transcription Factor in Live Cells Revealed by Fluorescence Microscopy and Computer Modeling.
000127594 260__ $$aWashington, DC$$bSoc.$$c2015
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000127594 520__ $$aThe c-Fos and c-Jun transcription factors, members of the activator protein 1 (AP-1) complex, form heterodimers and bind to DNA via a basic leucine zipper and regulate the cell cycle, apoptosis, differentiation, etc. Purified c-Jun leucine zipper fragments could also form stable homodimers, whereas c-Fos leucine zipper homodimers were found to be much less stable in earlier in vitro studies. The importance of c-Fos overexpression in tumors and the controversy in the literature concerning c-Fos homodimerization prompted us to investigate Fos homodimerization. Förster resonance energy transfer (FRET) and molecular brightness analysis of fluorescence correlation spectroscopy data from live HeLa cells transfected with fluorescent-protein-tagged c-Fos indicated that c-Fos formed homodimers. We developed a method to determine the absolute concentrations of transfected and endogenous c-Fos and c-Jun, which allowed us to determine dissociation constants of c-Fos homodimers (Kd = 6.7 ± 1.7 μM) and c-Fos-c-Jun heterodimers (on the order of 10 to 100 nM) from FRET titrations. Imaging fluorescence cross-correlation spectroscopy (SPIM-FCCS) and molecular dynamics modeling confirmed that c-Fos homodimers were stably associated and could bind to the chromatin. Our results establish c-Fos homodimers as a novel form of the AP-1 complex that may be an autonomous transcription factor in c-Fos-overexpressing tissues and could contribute to tumor development.
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000127594 650_7 $$2NLM Chemicals$$aChromatin
000127594 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-fos
000127594 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-jun
000127594 650_7 $$2NLM Chemicals$$aTranscription Factor AP-1
000127594 650_7 $$09007-49-2$$2NLM Chemicals$$aDNA
000127594 7001_ $$0P:(DE-He78)f19ec6784f8068e5d4b51b33afc7ae6a$$aKrieger, Jan Wolfgang$$b1$$udkfz
000127594 7001_ $$aKomáromi, István$$b2
000127594 7001_ $$0P:(DE-He78)ae1ffa194e5a8191ce2346491e4e828d$$aTóth, Katalin$$b3$$udkfz
000127594 7001_ $$aVámosi, György$$b4
000127594 773__ $$0PERI:(DE-600)1474919-1$$a10.1128/MCB.00346-15$$gVol. 35, no. 21, p. 3785 - 3798$$n21$$p3785 - 3798$$tMolecular and cellular biology$$v35$$x1098-5549$$y2015
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