Retinoic acid regulates aberrant nuclear localization of PML-RARα in acute promyelocytic leukemia cells

Karsten Weis, Sophie Rambaud, Catherine Lavau, Joop Jansen, Teresa Carvalho, Maria Carmo-Fonseca, Angus Lamond, Anne Dejean (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    639 Citations (Scopus)

    Abstract

    Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) translocation that fuses the retinoic acid receptor α (RARα) to a novel gene product, PML. The involvement of RARα is particularly intriguing in view of the efficient therapeutic effect of retinoic acid (RA) in this disease. In this report, we show that PML is specifically localized within a discrete subnuclear compartment corresponding to nuclear bodies recognized by patient autoimmune sera. In APL cells, the PML-RARα hybrid displays an abnormal localization and directs RXR and other nuclear antigens into aberrant structures that are tightly bound to chromatin. This suggests that the hybrid could exert a dominant negative effect by diverting a subset of proteins from their natural sites of action. Interestingly, treatment of APL cells with RA induces a complete relocalization of each of these proteins. We propose that the beneficial role of RA in promoting myeloid differentiation in APL might be related to its ability to restore a normal subnuclear organization.

    Original languageEnglish
    Pages (from-to)345-356
    Number of pages12
    JournalCell
    Volume76
    Issue number2
    DOIs
    Publication statusPublished - 28 Jan 1994

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology

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