Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Abstract

E-cadherin expression was previously shown to be activated by RB and c-myc speci®cally in epithelial cells, through interaction with the AP-2 transcription factor. Here we show that only a wild type c-myc gene, coding for the two c-Myc proteins c-Myc2 and c-Myc1, was able to transactivate the E-cadherin promoter, in contrast to c-Myc2 or c-Myc1 alone which strongly repressed E-cadherin in both epithelial cells and ®broblasts. In addition, overexpression of c-myc2 or cmyc1 inhibited c-myc and RB-mediated activation in a dose-dependent manner, suggesting that the ratio of the two c-Myc proteins is essential for transactivation. We also showed by using several mutants of the E-cadherin promoter, that the AP-2 binding sites were the main target of c-myc2-and c-myc1-mediated repression. AP-2-mediated inhibition was cell-type speci®c, as was the activation. Nevertheless, when high amounts of c-myc2 and c-myc1 were used, a second c-myc-mediated repression was observed, possibly mediated by the Inr sequence of the E-cadherin promoter. However, this repression was independent of cell type. Our results suggest a new way to regulate c-myc transcriptional activity by interfering with the ratio of the two c-myc proteins, which has already been found to be disrupted in vivo in several tumor types.

The Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Transactivates the Telomerase Reverse Transcriptase Promoter

“…Consequently, in the BJAB cell line, LANA-mediated fold activation was likely less dramatic because of this already strong endogenous activation mediated by Myc. Similarly, HEK 293T expresses the SV40 T-antigen, a promiscuous transactivator that has been shown to activate the human Myc promoter (68). In fact, endogenous activation of the hTERT promoter was 10-fold higher in HEK 293T relative to HEK 293 by transient transfection luciferase assay, suggesting that endogenous hTERT promoter activity was indeed up-regulated in the HEK 293T cell line (data not shown).…”

Activator Protein 2α Associates with Adenomatous Polyposis Coli/β-Catenin and Inhibits β-Catenin/T-cell Factor Transcriptional Activity in Colorectal Cancer Cells

“…We provide here the first evidence that APC is a direct binding partner of AP-2␣, but several other AP-2␣-interacting proteins have been identified, including retinoblastoma protein (16,31), Myc (17,19), SV-40 large T antigen (32), human T-cell leukemia virus type 1 (33), PC4 (34), poly(ADP-ribose) polymerase (18), KLF9, and KLF12 (35,36). Many of these AP-2␣-binding proteins are well established regulators of gene expression.…”

Revealing signaling pathway deregulation by using gene expression signatures and regulatory motif analysis

“…Indeed, it has been indicated that over-expression of E2F3 or Ras induces tumor invasion through interaction with AP-2α, a characteristic TF in the caspases pathway, in epithelial cells of bladder cancer [28]. It has also been shown that c-Myc represses AP-2α trans -activation [29]. Another pathway found to be affected for more than one signature was the AhR pathway, which was found to be significant for both the Myc and Ras gene signatures.…”