Characterization of the promoter of the human farnesyltransferase beta subunit and the impact of the transcription factor OCT-1 on its expression

Genomics. 2022 Mar;114(2):110314. doi: 10.1016/j.ygeno.2022.110314. Epub 2022 Feb 12.

Abstract

Farnesyltransferase (FTase) enables about 100 proteins to interact with cellular membranes by catalyzing the posttranslational addition of a farnesyl group. Farnesylated proteins provide important functions and inhibitors against the β-subunit of the heterodimer of FTase are intensively studied in clinical and preclinical trials. However, very little is known about the transcriptional regulation of the β-subunit. The examined promoter region of the human FTase β-subunit gene (FNTB) showed significant basal promoter activity in HEK-293 and in HeLa cells. We were able to locate the core promoter at -165 to -74. Ten potential binding sites of the transcription factor OCT-1 were detected. Three could be confirmed using EMSA super shift experiments. OCT-1 overexpression and knockdown confirmed it as an important regulator of FNTB expression. Our results provide a basis for further research on FNTB/OCT-1 regulation, its inhibitors and diseases influenced by both such as colon carcinoma or diabetes mellitus.

Keywords: FNTB; Farnesyltransferase; OCT-1; Promoter characterization; Regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases* / genetics
  • Alkyl and Aryl Transferases* / metabolism
  • Farnesyltranstransferase / genetics
  • Farnesyltranstransferase / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / metabolism
  • Promoter Regions, Genetic

Substances

  • Octamer Transcription Factor-1
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase