The Repertoire of Fos and Jun Proteins Expressed during the G1 Phase of the Cell Cycle Is Determined by the Duration of Mitogen-Activated Protein Kinase Activation

• DOI: 10.1128/mcb.19.1.330
• Publication Date: 2015-10-26T10:17:07Z
• Authors: Simon J. Cook; Natasha Aziz; Martin McMahon
• Keywords: JUNB; Immediate early gene; AP-1 transcription factor; Serum Response Element; c-jun

In Rat-1 fibroblasts nonmitogenic doses of lysophosphatidic acid (LPA) stimulate a transient activation mitogen-activated protein kinase (MAPK), whereas mitogenic elicit sustained response. This phase MAPK regulates cell fate decisions such as proliferation or differentiation, presumably by inducing program gene expression which is not observed in response to activation. We have examined the members AP-1 transcription factor complex stimulation with different LPA. c-Fos, c-Jun, and JunB are induced rapidly LPA stimulation, Fra-1 Fra-2 after significant lag. The c-Fos transient, JunB, Fra-1, sustained. early can be reconstituted LPA, but compared that doses. contrast, Fra-2, optimal c-Jun only induce DNA synthesis. LPA-stimulated inhibited MEK1 inhibitor PD098059, indicating Raf-MEK-MAPK cascade required for their expression. cells expressing conditionally active form Raf-1 (ΔRaf-1:ER), we selective, was sufficient but, interestingly, little no c-Jun. induction strongly buffering intracellular [Ca2+]. Moreover, although Raf calcium ionophores expression, synergistic combination ΔRaf-1:ER ionomycin. These results suggest kinetically distinct phases serve regulate components JunB. However, contrast case alone rather requires cooperation other signals Ca2+mobilization. Finally, identification genes selectively regulated activated suggests they candidates mediate certain effects Ras proteins oncogenic transformation.