Transcription factor TFE3 enhances cell cycle and cancer progression by binding to the hTERT promoter

Abstract

Abbreviations bp Base pair CCND1 Cyclin D1 FLI1 Friend leukemia integration 1 transcription factor hTERT Human telomerase reverse transcriptase IgG Immunoglobulin G MYC MYC proto-oncogene, BHLH transcription factor p27 Cyclin-dependent kinase inhibitor 1B p53 Tumor protein p53 Sp1 Sp1 transcription factor TERT Telomerase reverse transcriptase TF Transcription factor TFE3 Transcription factor binding to IGHM enhancer 3 TSS Transcription start site ZNF556 Zinc finger protein 556 Dear Editor, Telomeres are located at the ends of chromosomes and are essential for chromosome stability and replication. Furthermore, friend leukemia integration 1 (FLI1) specifically binds to novel transcription binding sites created by hTERT promoter mutations that frequently occur in tumors, thereby enhancing telomerase activity [ 7]. [...]identification of other upstream regulators of hTERT could enrich our knowledge on the regulatory hTERT network involved in tumor biology. Two TFs – transcription factor binding to IGHM enhancer 3 (TFE3) and zinc finger protein 556 (ZNF556) – exhibited particularly strong binding to the hTERT promoter (Figure 1A). Since TFE3 is known to be associated with the occurrence and progression of several tumors [ 9], we focused our analyses on this molecule, leaving ZNF556 for future studies. Besides analyzing the changes to hTERT, we looked at the expression of cell cycle-associated marker cyclin D1 (CCND1), since several regulators of hTERT activity have been reported to influence the cell cycle.