Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences.

Abstract

Transcription of the c-fos proto-oncogene is rapidly induced in the rat pheochromocytoma PC12 cell line by a wide variety of stimuli, including polypeptide growth factors, phorbol esters, and calcium ion fluxes. We have mapped the upstream sequence requirements for this activation in PC12 cells by analysis of promoter deletion mutants in a transient expression assay. Two distinct pathways of c-fos induction are defined that differ in their requirement for cis-acting DNA sequences. Calcium activation of c-fos transcription is dependent on a DNA element located approximately 60 base pairs upstream of the transcription start site. This region is highly conserved between human, mouse, and chicken c-fos genes and contains a sequence that resembles the consensus for a cyclic AMP response element. The dyad symmetry element at position -300, which is necessary for serum responsiveness of c-fos, appears to be unimportant for calcium activation of the gene. The dyad symmetry element is, however, an essential cis-acting sequence for c-fos inducibility by nerve growth factor, epidermal growth factor, fibroblast growth factor, and the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate. Studies in vivo and in vitro with various mutants of the dyad symmetry element indicate that c-fos activation by polypeptide growth factors and 12-O-tetradecanoyl phorbol-13-acetate is mediated by a common transcription factor, and that this factor is identical to the previously described serum response factor. In vitro DNA-binding assays suggest that the quantity of serum response factor-binding activity remains unchanged during c-fos transcriptional activation.Expression of the c-fos proto-oncogene is rapidly and transiently activated in a variety of mammalian cell types by a diverse set of stimuli, including serum, specific polypeptide growth factors, phorbol esters, neurotransmitters, and agents that elevate intracellular calcium and cyclic AMP (cAMP) (3,5,6,12,13,15,16,23,24,29,(32)(33)(34)

Association of lipoprotein lipase gene polymorphisms with obesity and type 2 diabetes in an Asian Indian population

“…À54 to À47), similar to the (TGACGTTT) of the c-fos gene promoter. 26 DNase I protection assays have revealed a footprint in the region extending approximately from nt À52 to À35. 27 The À53 substitution may affect the binding of Oct-1 to the octamer site or some of other transcription factors to the putative Ca 2 þ -responsive element.…”

Nuclear protein phosphorylation and growth control

“…Ca2+ mediates gene induction in response to membrane depolarization of various neuronal cell lines and this inducibility has been mapped to CRE-like elements in different promoters (Sheng et al, 1988;Nguyen et al, 1990). In addition, rapid phosphorylation of CREB at has been demonstrated in response to membrane stimulation (Sheng et al, 1991) (Sheng et al, 1991;Dash et al, 1991).…”

Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

“…Subsequently, it was found that SRF and/or SRF binding sites (CC(A/ T) 6 GG), termed CArG boxes, regulate expression of a wide variety of serum responsive genes (Changelian et al, 1989;Chavrier et al, 1989;Christy and Nathans, 1989;Latinkic et al, 1991;Latinkic and Lau, 1994;Treisman, 1990;Tsai-Morris et al, 1988). SRF also regulates transcription mediated by treatment of cells with neurotrophins (Sheng et al, 1988;Visvader et al, 1988), neurotransmitters and agents that raise intracellular calcium levels (Bading et al, 1993;McDonough et al, 1997;Misra et al, 1994), stress agents, and viral activators (Avantaggiati et al, 1993;Fujii et al, 1992Fujii et al, , 1994. A variety of experiments indicate that SRF is a key transcription factor controlling genes that are involved in cell cycle progression, di erentiation, and development (Arsenian et al, 1998;Croissant et al, 1996;Gauthier-Rouviere et al, 1991;Vandromme et al, 1992).…”