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Expression of many primary response cellular genes is observed during the early stages of transition from a resting G0 state to DNA synthesis. To identify gene products implicated in long-term response to growth factors, we have isolated genes sequentially activated several hours after serum stimulation of fibroblastic CCL39 cells. We report here the characterization of one of them as encoding the immunophilin of 56-59 kDa (FKBP-59), a component of the steroid receptor complex. FKBP-59 is encoded in several mammalian species by a unique gene located within the transition protein 2 gene locus. FKBP-59 mRNA is ubiquitously expressed at various levels in human organs. FKBP-59 gene activation in CCL39 fibroblasts requires protein synthesis during the first 2 h of stimulation, a period of time during which proto-oncogenes such as c-fos or c-jun are expressed. FKBP-59 mRNA degrades upon serum withdrawal and accumulates in proportion to the mitogenic strength of various purified growth factors. Its expression is reduced in CCL39 mutant-transformed cells or cells able to grow in low serum-containing medium, suggesting that FKBP-59 might participate in the negative feedback control to cell proliferation.
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