The oncoproteins c-Fos and
c-Jun are transcription factors that dimerize forming AP-1 complexes to selectively
regulate expression of target genes in the nucleus. c-Fos also associates to
endoplasmic reticulum to activate phospholipid metabolism. Our studies were
aimed at determining the thermodynamic properties of c-Fos that may be related
to its association to membrane. We used the monolayer technique to explore the
surface activity of c-Fos as well as some aspects of its interaction with phospholipids.
This simple, controlled system also helped us to establish the capacity of
c-Fos to modulate phospolipases A2, C and sphingomyelinase, and we
show that it does so through alteration of substrate packing. Complementary
studies using epifluorescence- and Brewster Angle Microscopy reinforce our
findings and enable visualization of the opposite effects of c-Fos on dilauroylphosphatidylcholine
and phosphatidylinositol diphosphate surface molecular organization. Finally,
we studied the association of c-Fos with c-Jun, concluding that it is greatly
stabilized by the interface as an equimolar entity.
The body of our results
provide a basis by which c-Fos may transduce molecular information at the
membrane level.
This work
was supported by FONCyT, CONICET, Fundación Antorchas, SeCyT-UNC and James S.
McDonnell Foundation.
