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

Philippe Dhordain, Olivier Albagli, Nicole Honore, Fabien Guidez, Danièle Lantoine, Michel Schmid, Hugues De The, Arthur Z Zelent, Marcel H M Koken

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6240-6250
Number of pages11
JournalOncogene
Volume19
Issue number54
DOIs
StatePublished - Dec 14 2000
Externally publishedYes

Fingerprint

Zinc Fingers
Oncogenes
Acute Promyelocytic Leukemia
Non-Hodgkin's Lymphoma
Proteins
Yeasts
Two-Hybrid System Techniques
Histone Deacetylases
CHO Cells
Myeloid Cells
Immunoprecipitation
Carcinogenesis
Transcription Factors
Growth
Genes
BTB-POZ Domain

Keywords

  • APL
  • Non Hodgkin lymphoma
  • Nuclear body
  • PML

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Dhordain, P., Albagli, O., Honore, N., Guidez, F., Lantoine, D., Schmid, M., ... Koken, M. H. M. (2000). Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF. Oncogene, 19(54), 6240-6250. https://doi.org/10.1038/sj.onc.1203976

Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF. / Dhordain, Philippe; Albagli, Olivier; Honore, Nicole; Guidez, Fabien; Lantoine, Danièle; Schmid, Michel; De The, Hugues; Zelent, Arthur Z; Koken, Marcel H M.

In: Oncogene, Vol. 19, No. 54, 14.12.2000, p. 6240-6250.

Research output: Contribution to journalArticle

Dhordain, P, Albagli, O, Honore, N, Guidez, F, Lantoine, D, Schmid, M, De The, H, Zelent, AZ & Koken, MHM 2000, 'Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF', Oncogene, vol. 19, no. 54, pp. 6240-6250. https://doi.org/10.1038/sj.onc.1203976
Dhordain, Philippe ; Albagli, Olivier ; Honore, Nicole ; Guidez, Fabien ; Lantoine, Danièle ; Schmid, Michel ; De The, Hugues ; Zelent, Arthur Z ; Koken, Marcel H M. / Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF. In: Oncogene. 2000 ; Vol. 19, No. 54. pp. 6240-6250.
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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 Kr{\"u}ppel 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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