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

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-00408483
Contributor : Marie Laure Haon Connect in order to contact the contributor
Submitted on : Thursday, July 30, 2009 - 5:14:11 PM
Last modification on : Thursday, April 7, 2022 - 10:10:11 AM

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Hanane Boukarabila, Andrew J Saurin, Eric Batsché, Noushine Mossadegh, Maarten van Lohuizen, et al.. The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation.. Genes and Development, Cold Spring Harbor Laboratory Press, 2009, 23 (10), pp.1195-206. ⟨10.1101/gad.512009⟩. ⟨hal-00408483⟩

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