Avian erythroleukemia: A model for corepressor function in cancer

Luc E.G. Rietveld, Eric Caldenhoven, Hendrik G. Stunnenberg

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)

Abstract

Transcriptional regulation at the level of chromatin plays crucial roles during eukaryotic development and differentiation. A plethora of studies revealed that the acetylation status of histones is controlled by multi-protein complexes containing (de)acetylase activities. In the current model, histone deacetylases and acetyltransferases are recruited to chromatin by DNA-bound repressors and activators, respectively. Shifting the balance between deacetylation, i.e. repressive chromatin and acetylation, i.e. active chromatin can lead to aberrant gene transcription and cancer. In human acute promyelocytic leukemia (APL) and avian erythroleukemia (AEL), chromosomal translocations and/or mutations in nuclear hormone receptors, RARα [NR1B1] and TRα [NR1A1], yielded oncoproteins that deregulate transcription and alter chromatin structure. The oncogenic receptors are locked in their 'off' mode thereby constitutively repressing transcription of genes that are critical for differentiation of hematopoietic cells. AEL involves an oncogenic version of the chicken TRα, v-ErbA. Apart from repression by v-ErbA via recruitment of corepressor complexes, other repressors and corepressors appear to be involved in repression of v-ErbA target genes, such as carbonic anhydrase II (CAII). Reactivation of repressed genes in APL and AEL by chromatin modifying agents such as inhibitors of histone deacetylase or of methylation provides new therapeutic strategies in the treatment of acute myeloid leukemia.

Original languageEnglish
Pages (from-to)3100-3109
Number of pages10
JournalOncogene
Volume20
Issue number24
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Carbonic anhydrase II
  • Corepressor
  • Erythroleukemia
  • Histone deacetylase
  • Methylation
  • v-ErbA

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