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  • Original Paper
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Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF

Oncogene volume 19, pages 6240–6250 (2000)Cite this article

Abstract

Most acute promyelocytic leukemia (APL) cases are associated with recurrent translocations between the gene of retinoic receptor alpha and that of PML (t(15;17)) or PLZF (t(11;17)). PML localizes onto discrete intranuclear domains, the PML-nuclear bodies, and displays anti-oncogenic and pro-apoptotic properties. PLZF encodes a transcription factor belonging to the POZ/domain and Krüppel zinc finger (POK) family which interacts directly with PML. PLZF is related to another POK protein, LAZ3(BCL6), which is structurally altered, and presumably misexpressed, in many non-Hodgkin lymphoma (NHL) cases. PLZF and LAZ3 share many functional properties: both inhibit cell growth, concentrate into punctated nuclear subdomains and are sequence-specific transcriptional repressors recruiting a histone deacetylase-repressing complex. Given these similarities, we tested whether both proteins could be targeted by each other. Here, LAZ3 and PLZF are shown to colocalize onto nuclear dots. Moreover, truncated derivatives of one protein, which display a diffuse nuclear localization, are recruited onto nuclear dots by the full-length other. The colocalization and the reciprocal ‘rescue’ is the result of a direct interaction between LAZ3 and PLZF, as indicated by yeast two hybrid assays, in vitro immunoprecipitations, and GST pull down experiments. In contrast to LAZ3 homomerization, LAZ3/PLZF heteromerization in yeast does not solely depend on POZ/POZ contacts but rather also relies on interactions between the two zinc finger regions and ‘cross’ contacts between the zinc finger region and the POZ domain of each partner. Likewise, LAZ3 shows some colocalization with the PLZF partner PML upon stable overexpression of both proteins in CHO cells and interacts with PML in yeast. Finally, endogenous LAZ3 and PLZF are co-induced and partially colocalized in myeloid MDS cells. These data indicate that a physical interaction between LAZ3 and PLZF underlies their simultaneous recruitment onto multiproteic nuclear complexes, presumably involved in transcriptional silencing and whose integrity (for APL) and/or function (for APL and NHL) may be altered in oncogenesis.

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Acknowledgements

This work is dedicated to the memory of Philippe Dhordain. We would like to thank LPH for photograpy, Christel Doliger for confocal microscopy analysis, and Gustavo Linares-Cruz and Guy Millot for help with CCD camera imaging. Jean-Pierre Kerckaert is thanked for support, and Dominiqe Leprince for stimulating discussions. Jonathan Licht and Chen Zhu are acknowledged for providing us with the PLZF monoclonal antibody and some PLZF constructs. Finally, we want to thank all our colleagues for help and some nice discussions. We thank ‘L'Association pour la Recherche contre le Cancer (ARC), ‘La Fondation pour le Recherche Médicale (FRM)’ and ‘La Ligue Contre le Cancer’ for their financial support. This work was also supported by grants from INSERM and CNRS.

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Author notes

  1. Philippe Dhordain and Olivier Albagli: P Dhordain and O Albagli contributed equally to this work

Authors and Affiliations

  1. INSERM U524, IRCL, Place de Verdun, Lille, 59045, France

    Philippe Dhordain, Olivier Albagli & Danièle Lantoine

  2. CNRS UPR 9051 (Unité conventionnée par l'Université Paris 7), Hôpital St. Louis, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France

    Nicole Honore, Hugues De The & Marcel HM Koken

  3. Leukemia Research Fund Center at the Institute of Cancer Research, Chester Beatty Laboratories, London, UK

    Fabien Guidez & Arthur Zelent

  4. INSERM U462, Hôpital St. Louis, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France

    Michel Schmid

  5. UPR 1983, 7 rue Guy Noquet-BP8-94801 Villejuif, France

    Olivier Albagli

  6. Station de Biologie Marine du MNHN BP225-29182, Concarneau, France

    Marcel HM Koken

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Dhordain, P., Albagli, O., Honore, N. et al. Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF. Oncogene 19, 6240–6250 (2000). https://doi.org/10.1038/sj.onc.1203976

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