TY - JOUR
T1 - Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF
AU - Dhordain, Philippe
AU - Albagli, Olivier
AU - Honore, Nicole
AU - Guidez, Fabien
AU - Lantoine, Danièle
AU - Schmid, Michel
AU - De The, Hugues
AU - Zelent, Arthur
AU - Koken, Marcel H.M.
N1 - Funding Information:
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.
PY - 2000/12/14
Y1 - 2000/12/14
N2 - 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.
AB - 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.
KW - APL
KW - Non Hodgkin lymphoma
KW - Nuclear body
KW - PML
UR - http://www.scopus.com/inward/record.url?scp=0034649504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034649504&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1203976
DO - 10.1038/sj.onc.1203976
M3 - Article
C2 - 11175338
AN - SCOPUS:0034649504
VL - 19
SP - 6240
EP - 6250
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 54
ER -
