Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies

M. H M Koken, A. Reid, F. Quignon, M. K. Chelbi-Alix, J. M. Davies, J. H S Kabarowski, J. Zhu, S. Dong, S. J. Chen, Z. Chen, C. C. Tan, J. Licht, S. Waxman, H. De The, Arthur Z Zelent

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.

Original languageEnglish (US)
Pages (from-to)10255-10260
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number19
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Retinoic Acid Receptors
Leukemia
Acute Promyelocytic Leukemia
Proteins
Nuclear Proteins
Interferons
Genes

Keywords

  • Acute promyelocytic leukemia
  • Interferon
  • Nuclear matrix
  • Translocation
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. / Koken, M. H M; Reid, A.; Quignon, F.; Chelbi-Alix, M. K.; Davies, J. M.; Kabarowski, J. H S; Zhu, J.; Dong, S.; Chen, S. J.; Chen, Z.; Tan, C. C.; Licht, J.; Waxman, S.; De The, H.; Zelent, Arthur Z.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 19, 1997, p. 10255-10260.

Research output: Contribution to journalArticle

Koken, MHM, Reid, A, Quignon, F, Chelbi-Alix, MK, Davies, JM, Kabarowski, JHS, Zhu, J, Dong, S, Chen, SJ, Chen, Z, Tan, CC, Licht, J, Waxman, S, De The, H & Zelent, AZ 1997, 'Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies', Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 19, pp. 10255-10260. https://doi.org/10.1073/pnas.94.19.10255
Koken, M. H M ; Reid, A. ; Quignon, F. ; Chelbi-Alix, M. K. ; Davies, J. M. ; Kabarowski, J. H S ; Zhu, J. ; Dong, S. ; Chen, S. J. ; Chen, Z. ; Tan, C. C. ; Licht, J. ; Waxman, S. ; De The, H. ; Zelent, Arthur Z. / Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 19. pp. 10255-10260.
@article{c80d70a5cc264fce9989359f3911ec9f,
title = "Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies",
abstract = "In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.",
keywords = "Acute promyelocytic leukemia, Interferon, Nuclear matrix, Translocation, Yeast two-hybrid",
author = "Koken, {M. H M} and A. Reid and F. Quignon and Chelbi-Alix, {M. K.} and Davies, {J. M.} and Kabarowski, {J. H S} and J. Zhu and S. Dong and Chen, {S. J.} and Z. Chen and Tan, {C. C.} and J. Licht and S. Waxman and {De The}, H. and Zelent, {Arthur Z}",
year = "1997",
doi = "10.1073/pnas.94.19.10255",
language = "English (US)",
volume = "94",
pages = "10255--10260",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "19",

}

TY - JOUR

T1 - Leukemia-associated retinoic acid receptor fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies

AU - Koken, M. H M

AU - Reid, A.

AU - Quignon, F.

AU - Chelbi-Alix, M. K.

AU - Davies, J. M.

AU - Kabarowski, J. H S

AU - Zhu, J.

AU - Dong, S.

AU - Chen, S. J.

AU - Chen, Z.

AU - Tan, C. C.

AU - Licht, J.

AU - Waxman, S.

AU - De The, H.

AU - Zelent, Arthur Z

PY - 1997

Y1 - 1997

N2 - In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.

AB - In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.

KW - Acute promyelocytic leukemia

KW - Interferon

KW - Nuclear matrix

KW - Translocation

KW - Yeast two-hybrid

UR - http://www.scopus.com/inward/record.url?scp=0030885596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030885596&partnerID=8YFLogxK

U2 - 10.1073/pnas.94.19.10255

DO - 10.1073/pnas.94.19.10255

M3 - Article

VL - 94

SP - 10255

EP - 10260

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 19

ER -