title: Cell proliferation and cell cycle progression are not impaired in fibroblasts and ES cells lacking c-Fos.
abstract: The transcription factor AP-1 is thought to play an important role in the control of cell proliferation, but the function of individual Fos and Jun family members is a largely unresolved issue. To directly analyse the function of c-Fos in the control of cell proliferation we have used embryonic stem (ES) cells and fibroblasts lacking c-Fos due to a disruption of the c-fos gene by homologous recombination. Our results demonstrate that proliferation of normally cycling cells and reentry of quiescent cells into the cell cycle following serum stimulation are not c-Fos-dependent and occur with similar efficiency in c-fos-/- and control cells. We also show that there is no compensatory overexpression or activation of other known Fos or Jun family members. On the contrary, the c-fos-/- cells showed a reduced induction of fra-1 after serum stimulation which is in agreement with the previous identification of fra-1 as a c-Fos target gene. Comparison of the AP-1 binding and transactivation activities in c-fos-/- and +/+ fibroblasts by electrophoretic mobility antibody supershift and CAT assays suggests that c-Fos is not a major component of AP-1 complexes in these cells. It is therefore conceivable that the lack of any detectable effect on cell proliferation in c-fos-/- cells might be due to a functional redundancy among the different AP-1 family members.
authors: Institut für Molekularbiologie und Tumorforschung (IMT), Marburg, Germany.
authors: S
authors: S
authors: Brüsselbach
authors: U
authors: U
authors: Möhle-Steinlein
authors: Z Q
authors: ZQ
authors: Wang
authors: M
authors: M
authors: Schreiber
authors: F C
authors: FC
authors: Lucibello
authors: R
authors: R
authors: Müller
authors: E F
authors: EF
authors: Wagner
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D013234:Stem Cells / Q000166:cytology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1