Multiple cis-Elements Mediate the Transcriptional Activation of Human fra-1 by 12-O-Tetradecanoylphorbol-13-acetate in Bronchial Epithelial Cells

Adiseshaiah, Pavan P.; Papaiahgari, Srinivas; Vuong, Hue; Kalvakolanu, Dhananjaya V.; Reddy, Sekhar P.

doi:10.1074/jbc.m303505200

Cited by 38 publications

(57 citation statements)

References 32 publications

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“…Previous studies (Brusselbach et al, 1995;Schreiber et al, 1997), including ours (Adiseshaiah et al, 2003), have reported a critical role for c-Jun in mediating the induction of FRA-1 by mitogenic stimuli. However, the effects of SRF and TCFs, and ATF1 and CREB in mediating FRA-1 transcription by extracellular stimuli have not yet been determined.…”

Section: Fra-1 Transcriptionmentioning

confidence: 48%

“…Recently, we have shown that the À318 TRE of the FRA-1 promoter is necessary for its TPAinducible expression in A549 cells (Adiseshaiah et al, 2003). We have shown that c-JUN and FRA-2 proteins are recruited to the endogenous FRA-1 promoter following TPA stimulation.…”

Section: Resultsmentioning

confidence: 90%

“…The specificity of these complexes was analysed by competition assays using the unlabeled TCF-CArG-ATF (self) and other oligos: consensus TRE, consensus GC-box and the ATF oligo (see Figure 4a for sequence). Only the functional cis-acting elements, EBS, GC box (or Sp1 site) and TRE, located between -379 to À283 bp, are shown (see Adiseshaiah et al, 2003). After 18-24 h, cells were serum-starved for 24 h and treated with vehicle (DMSO) or TPA (100 ng/ml) for 5 h. The firefly luciferase activity was normalized to that of Renilla luciferase, and the fold-activation by TPA was calculated using the values of unstimulated cells as 1.0 (n ¼ 3).…”

Section: Resultsmentioning

confidence: 99%

“…We have shown earlier the recruitment of c-Jun to the endogenous FRA-1 promoter in response to TPA treatment (Adiseshaiah et al, 2003). To determine whether SRF, Elk1, CREB and ATF1 are similarly recruited to the promoter in vivo, we performed a ChIP assay using the crosslinked chromatin fragments prepared from control and TPA-stimulated A549 cells ( Figure 6).…”

Section: Tcfmentioning

confidence: 99%

“…We have recently demonstrated that the -379 to þ 32 bp genomic sequence, devoid of introns, contains sufficient information to drive FRA-1 transcription in response to diverse stimuli in several lung cell types (Adiseshaiah et al, 2003). The TPA inducible transcription of FRA-1 is mainly dependent on a TRE located at À318.…”

Section: Introductionmentioning

confidence: 99%

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Mitogen regulated induction of FRA-1 proto-oncogene is controlled by the transcription factors binding to both serum and TPA response elements

et al. 2005

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FRA-1, a member of the FOS family of transcription factors, is overexpressed in a variety of human tumors, and contributes to tumor progression. In addition to mitogens, various toxicants and carcinogens persistently induce FRA-1 expression in vitro and in vivo. Although the mitogen induced expression of c-FOS is relatively well understood, it is poorly defined in the case of FRA-1. Our recent analysis of the FRA-1 promoter has shown a critical role for a TRE located at À318 in mediating the TPA-induced expression. The À379 to À283 bp promoter segment containing a critical TRE (À318), however, is insufficient for the induction of FRA-1 promoter. Here, we show that a 40-bp (À276/À237) segment, comprising a TCF binding site and the CArG box (collectively known as serum response element, SRE), and an ATF site, is also necessary for the FRA-1 induction by TPA and EGF. Interestingly, the À283 to þ 32 bp FRA-1 promoter fragment containing an SRE and an ATF site alone was also insufficient to confer TPA sensitivity to a reporter gene. However, in association with the À318 TRE, the SRE and ATF sites imparted a strong TPA-inducibility to the reporter. Similarly, EGF also required these motifs for the full induction of this gene. Using ChIP assays we show that, in contrast to c-Jun, SRF, Elk1, ATF1 and CREB proteins bind to SRE and ATF sites of the FRA-1 promoter, constitutively. RNAi-mediated knockdown of endogenous SRF, ELK1 and c-JUN protein expression significantly reduced TPA-stimulated FRA-1 promoter activity. Thus, a bipartite enhancer formed by an upstream TRE and the downstream SRE and ATF sites and the cognate factors is necessary and sufficient for the regulation of FRA-1 in response to mitogens.

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Section: Fra-1 Transcriptionmentioning

confidence: 48%

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Tcfmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitogen regulated induction of FRA-1 proto-oncogene is controlled by the transcription factors binding to both serum and TPA response elements

et al. 2005

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Mutant p53 and ELK1 co‐drive FRA‐1 expression to induce metastasis in breast cancer

Hu,

Wang,

et al. 2023

FEBS Letters

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Tumor‐associated p53 mutations induce activities different from wild‐type p53, thus causing loss of the protein's tumor inhibition function. The cells carrying p53 mutations have more aggressive characteristics related to invasion, metastasis, proliferation, and cell survival. By comparing the gene expression profiles of mutant p53 (mutp53) and mutp53 silenced cohorts, we found that FOS‐related antigen‐1 (FRA‐1), which is encoded by FOSL1, is a potential effector of mutp53‐mediated metastasis. We demonstrate that the expression of FRA‐1, a gatekeeper of mesenchymal–epithelial transition, is elevated in the presence of p53 mutations. Mechanistically, mutant p53 cooperates with the transcription factor ELK1 in binding and activating the promoter of FOSL1, thus fostering lung metastasis. This study reveals new insights into how mutant p53 contributes to metastasis in breast cancer.

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A Fra‐1‐dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion

Adiseshaiah

Vaz

Machireddy

et al. 2008

Journal Cellular Physiology

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We and others have shown a persistently high induction of Fra-1 transcription factor (a dimeric partner of AP-1) levels by respiratory carcinogens in pulmonary epithelial cells. Fra-1 is frequently overexpressed in various human tumors and cancer cells. We have recently shown that Fra-1 significantly promotes growth, motility, and invasion of human pulmonary epithelial cells, the precise molecular mechanisms by which this enhancement occurs are unclear. Because matrix metalloproteinases (MMPs) play key roles in wound healing and lung tumor metastasis, we tested the hypothesis that Fra-1 promotes lung epithelial cell motility and invasion via MMP activation. We show here that MMP-9 and MMP-2 activated signaling plays a critical role in regulating Fra-1-induced lung epithelial cell growth and invasion. Ectopic Fra-1 markedly stimulates MMP-2 and MMP-9 mRNA expression. Inhibition of MMP-2 and MMP-9 activity significantly attenuated Fra-1-driven cell motility and invasion. Furthermore, Fra-1 induced EGFR phosphorylation in an MMPdependent manner, and an EGFR-specific inhibitor was able to block Fra-1-enhanced cell motility and invasion. Taken together, our data suggest that Fra-1 enhances lung cancer epithelial cell motility and invasion by inducing the activity of MMPs, in particular MMP-2 and MMP-9, and EGFRactivated signaling.

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Multiple cis-Elements Mediate the Transcriptional Activation of Human fra-1 by 12-O-Tetradecanoylphorbol-13-acetate in Bronchial Epithelial Cells

Cited by 38 publications

References 32 publications

Mitogen regulated induction of FRA-1 proto-oncogene is controlled by the transcription factors binding to both serum and TPA response elements

Mitogen regulated induction of FRA-1 proto-oncogene is controlled by the transcription factors binding to both serum and TPA response elements

Mutant p53 and ELK1 co‐drive FRA‐1 expression to induce metastasis in breast cancer

A Fra‐1‐dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion

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