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@ARTICLE{Szalki:127594,
author = {N. Szalóki and J. W. Krieger$^*$ and I. Komáromi and K.
Tóth$^*$ and G. Vámosi},
title = {{E}vidence for {H}omodimerization of the c-{F}os
{T}ranscription {F}actor in {L}ive {C}ells {R}evealed by
{F}luorescence {M}icroscopy and {C}omputer {M}odeling.},
journal = {Molecular and cellular biology},
volume = {35},
number = {21},
issn = {1098-5549},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DKFZ-2017-03617},
pages = {3785 - 3798},
year = {2015},
abstract = {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.},
keywords = {Chromatin (NLM Chemicals) / Proto-Oncogene Proteins c-fos
(NLM Chemicals) / Proto-Oncogene Proteins c-jun (NLM
Chemicals) / Transcription Factor AP-1 (NLM Chemicals) / DNA
(NLM Chemicals)},
cin = {B160},
ddc = {570},
cid = {I:(DE-He78)B160-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26303532},
pmc = {pmc:PMC4589601},
doi = {10.1128/MCB.00346-15},
url = {https://inrepo02.dkfz.de/record/127594},
}