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c‐Fos activates phospholipid metabolism in events associated to growth and differentiation
Author(s) -
Caputto B. L.,
Gil G. A.,
Portal M. M.,
Borioli G. A.,
Renner M. L.,
Guido M. E.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.3_3.x
Subject(s) - neurite , phospholipid , c fos , microbiology and biotechnology , immediate early gene , biology , transcription factor , protein biosynthesis , messenger rna , cell growth , cellular differentiation , transcription (linguistics) , gene expression , biochemistry , gene , in vitro , membrane , linguistics , philosophy
32 P phospholipid labelling increases in quiescent fibroblasts stimulated with serum to re‐enter growth. This stimulation of phospholipid synthesis shows two waves that depend on the transcription and translation of the immediate early gene c‐fos. The time‐course pattern of c‐Fos protein expression resembles the activation pattern of phospholipid synthesis ( The FASEB J , January 52001, 10.1096/fj.00‐0446fje). NGF‐treatment of PC12 cells promotes a strong increase in the expression of c‐Fos and enhances phospholipid synthesis in a c‐Fos‐concentration‐dependent way. Specifically blocking Fos expression with a c‐Fos mRNA antisense oligonucleotide impairs activation of phospholipid synthesis and also greatly inhibits cell differentiation. By contrast, inhibition of Fos degradation in NGF‐treated cells significantly increases c‐Fos content, phospholipid synthesis and neurite elongation. Blocking nuclear import of c‐Fos (AP‐1) at the initiation of NGF treatment completely blocks neurite formation. However, if c‐Fos nuclear import is blocked 16 h after addition of NGF to the cell cultures, neurite elongation continues almost normally. These results indicate that c‐Fos has a dual function in developing cells: it first releases the nuclear program for differentiation and then sustains growth by activating key components required for membrane genesis, in the cytoplasm. The mechanisms underlying this novel regulatory activity of c‐Fos on phospholipid synthesis, that is independent of its transcription factor activity, are being studied. Acknowledgements: Financed by Beca Carrillo‐Oñativia, FONCyT, Agencia Córdoba. Ciencia (CONICOR), SeCyT‐UNC, and CONICET.