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c‐Fos associates with the endoplasmic reticulum and activates phospholipid metabolism
Author(s) -
BUSSOLINO D.F.,
GUIDO M.E.,
GIL G.A.,
BORIOLI G.A.,
RENNER M.L.,
GRABOIS V.R.,
CONDE C.B.,
CAPUTTO B.L.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0446fje
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , phospholipid , signal transduction , transcription factor , c fos , biology , biochemistry , gene expression , chemistry , membrane , gene
c‐Fos, a transcription factor that constitutes DNA‐binding AP‐1 complexes, regulates gene expression that promotes long‐lasting cellular changes. We show that, in addition to its transcription factor activity, c‐Fos regulates the metabolism of phospholipids cytoplasmically by an AP‐1‐independent activity. Two waves of c‐Fos expression that promote subsequent waves of stimulation of 32 P‐orthophosphate incorporation into phospholipids are evidenced in quiescent cultured fibroblasts induced to re‐enter the cell cycle. The first wave of c‐Fos expression peaks at 7.5 min and returns to control levels by 15 min. The second wave starts by 30 min and remains elevated at 120 min. In the first wave, the lipids that incorporate 32 P are predominantly second‐messenger polyphosphoinositides (PIP, PIP 2 , PIP 3 ); whereas in the second wave, membrane‐biogenesis‐related lipids (PI, PE, PA), become radioactive. Both waves of phospholipid activation depend on c‐Fos expression. It is interesting that a peptide that blocks AP‐1 nuclear import does not affect phospholipid activation. Immunocytochemical examination showed c‐Fos immunoreactivity associated to the endoplasmic reticulum. We conclude that c‐Fos, rapidly induced upon cell stimulation, associates to the endoplasmic reticulum where it first regulates the synthesis/ replenishment of phospholipids required for signal transduction pathways and subsequently regulates enzymes involved in the genesis of new membrane necessary for cell growth.