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The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation.

Ectopic repression of retinoic acid (RA) receptor target genes by PML/RARA and PLZF/RARA fusion proteins through aberrant recruitment of nuclear corepressor complexes drives cellular transformation and acute promyelocytic leukemia (APL) development. In the case of PML/RARA, this repression can be reversed through treatment with all-trans RA (ATRA), leading to leukemic remission. However, PLZF/RARA ectopic repression is insensitive to ATRA, resulting in persistence of the leukemic diseased state after treatment, a phenomenon that is still poorly understood. Here we show that, like PML/RARA, PLZF/RARA expression leads to recruitment of the Polycomb-repressive complex 2 (PRC2) Polycomb group (PcG) complex to RA response elements. However, unlike PML/RARA, PLZF/RARA directly interacts with the PcG protein Bmi-1 and forms a stable component of the PRC1 PcG complex, resulting in PLZF/RARA-dependent ectopic recruitment of PRC1 to RA response elements. Upon treatment with ATRA, ectopic recruitment of PRC2 by either PML/RARA or PLZF/RARA is lost, whereas PRC1 recruited by PLZF/RARA remains, resulting in persistent RA-insensitive gene repression. We further show that Bmi-1 is essential for the PLZF/RARA cellular transformation property and implicates a central role for PRC1 in PLZF/RARA-mediated myeloid leukemic development.

Pubmed ID: 19451220


  • Boukarabila H
  • Saurin AJ
  • Batsché E
  • Mossadegh N
  • van Lohuizen M
  • Otte AP
  • Pradel J
  • Muchardt C
  • Sieweke M
  • Duprez E


Genes & development

Publication Data

May 15, 2009

Associated Grants


Mesh Terms

  • Antineoplastic Agents
  • Cell Transformation, Neoplastic
  • Chromatin
  • Humans
  • Leukemia
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Tretinoin
  • U937 Cells