Trim24 (Tif1a): An essential 'brake' for retinoic acid-induced transcription to prevent liver cancer

Konstantin Khetchoumian, Marius Teletin, Johan Tisserand, Benjamin Herquel, Khalid Ouararhni, Régine Losson*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

30 Citations (Scopus)

Abstract

Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RARa, b and g isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1α) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24-/-, but not Trim24 -/-Rara+/-, mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis.

Original languageEnglish
Pages (from-to)3647-3652
Number of pages6
JournalCell Cycle
Volume7
Issue number23
DOIs
Publication statusPublished - 1 Dec 2008
Externally publishedYes

Keywords

  • Hepatocarcinogenesis
  • Knockout
  • Mouse model
  • Proliferation
  • Quiescence
  • Retinoic acid receptor alpha
  • TRIM24/TIF1α
  • Transcriptional repression

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