Transcriptional regulation of the human tumor suppressor p14 ARF by E2F1, E2F2, E2F3, and Sp1-like factors

Tiziana Parisi, Alessandra Pollice, Antonio Di Cristofano, Viola Calabrò, Girolama La Mantia

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The human ARF/INK4a locus encodes two cell cycle inhibitors, p16INK4a and p14ARF, by using separate promoters. A variety of mitogenic stimuli upregulate ARF but a direct modulation at the transcriptional level has been reported only for E2F-1. We show here that the ARF promoter is strongly responsive also to E2F2 and E2F3, thus providing a strong support to their suggested role in the induction of apoptosis. Through the usage of both deletion mutants and/or site-directed mutants, we surprisingly found that none of the four putative E2F consensus sites is strictly necessary for the upregulation of ARF expression, as a minimal deletion mutant, lacking all the putative E2F binding sites, is still transactivated by E2F. Moreover, our data suggest that the ARF promoter is regulated by E2F through both direct binding to the promoter sequences and indirectly, probably by being tethered to the ARF promoter by Sp1-like factors.

Original languageEnglish (US)
Pages (from-to)1138-1145
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume291
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Tumor Suppressor Protein p14ARF
Tumors
Up-Regulation
Binding Sites
Cells
Modulation
Apoptosis
Neoplasms
Cell Cycle

Keywords

  • Apoptosis
  • E2F
  • Human p14ARF
  • Sp1-like factors
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Transcriptional regulation of the human tumor suppressor p14 ARF by E2F1, E2F2, E2F3, and Sp1-like factors. / Parisi, Tiziana; Pollice, Alessandra; Di Cristofano, Antonio; Calabrò, Viola; La Mantia, Girolama.

In: Biochemical and Biophysical Research Communications, Vol. 291, No. 5, 2002, p. 1138-1145.

Research output: Contribution to journalArticle

Parisi, Tiziana ; Pollice, Alessandra ; Di Cristofano, Antonio ; Calabrò, Viola ; La Mantia, Girolama. / Transcriptional regulation of the human tumor suppressor p14 ARF by E2F1, E2F2, E2F3, and Sp1-like factors. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 291, No. 5. pp. 1138-1145.
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