Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation

Clara Nervi, E. Christine Poindexter, Francesco Grignani, Pier Paolo Pandolfi, Francesco Lo Coco, Giuseppe Avvisati, Pier Giuseppe Pelicci, Anton M. Jetten

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RARα locus. The resulting chimeric gene encodes for a putative PML-RARα fusion protein. PML is a putative transcriptional factor and RARα is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RARα protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RARα. The introduction of the expression vector PSG5/PML-RARα into COS-1 cells led to high levels of expression of the PML-RARα fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RARα receptor. The PML-RARα fusion protein, but not the RARα, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RARα product was also found as a high molecular complex. The interaction of the PML-RARα with itself or with other nuclear proteins may be important in understanding the role of the PML-RARα fusion protein in promyelocytic leukemogenesis.

Original languageEnglish
Pages (from-to)3687-3692
Number of pages6
JournalCancer Research
Volume52
Issue number13
Publication statusPublished - Jul 1 1992

Fingerprint

Acute Promyelocytic Leukemia
Proteins
Retinoids
Genetic Translocation
Retinoic Acid Receptors
COS Cells
Nuclear Proteins
Tretinoin
Genes
Molecular Weight
High Pressure Liquid Chromatography
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nervi, C., Poindexter, E. C., Grignani, F., Pandolfi, P. P., Lo Coco, F., Avvisati, G., ... Jetten, A. M. (1992). Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation. Cancer Research, 52(13), 3687-3692.

Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation. / Nervi, Clara; Poindexter, E. Christine; Grignani, Francesco; Pandolfi, Pier Paolo; Lo Coco, Francesco; Avvisati, Giuseppe; Pelicci, Pier Giuseppe; Jetten, Anton M.

In: Cancer Research, Vol. 52, No. 13, 01.07.1992, p. 3687-3692.

Research output: Contribution to journalArticle

Nervi, C, Poindexter, EC, Grignani, F, Pandolfi, PP, Lo Coco, F, Avvisati, G, Pelicci, PG & Jetten, AM 1992, 'Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation', Cancer Research, vol. 52, no. 13, pp. 3687-3692.
Nervi C, Poindexter EC, Grignani F, Pandolfi PP, Lo Coco F, Avvisati G et al. Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation. Cancer Research. 1992 Jul 1;52(13):3687-3692.
Nervi, Clara ; Poindexter, E. Christine ; Grignani, Francesco ; Pandolfi, Pier Paolo ; Lo Coco, Francesco ; Avvisati, Giuseppe ; Pelicci, Pier Giuseppe ; Jetten, Anton M. / Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation. In: Cancer Research. 1992 ; Vol. 52, No. 13. pp. 3687-3692.
@article{e041d78cf1e34a6d8230b70edeb38c3a,
title = "Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation",
abstract = "The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RARα locus. The resulting chimeric gene encodes for a putative PML-RARα fusion protein. PML is a putative transcriptional factor and RARα is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RARα protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RARα. The introduction of the expression vector PSG5/PML-RARα into COS-1 cells led to high levels of expression of the PML-RARα fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RARα receptor. The PML-RARα fusion protein, but not the RARα, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RARα product was also found as a high molecular complex. The interaction of the PML-RARα with itself or with other nuclear proteins may be important in understanding the role of the PML-RARα fusion protein in promyelocytic leukemogenesis.",
author = "Clara Nervi and Poindexter, {E. Christine} and Francesco Grignani and Pandolfi, {Pier Paolo} and {Lo Coco}, Francesco and Giuseppe Avvisati and Pelicci, {Pier Giuseppe} and Jetten, {Anton M.}",
year = "1992",
month = "7",
day = "1",
language = "English",
volume = "52",
pages = "3687--3692",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "13",

}

TY - JOUR

T1 - Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation

AU - Nervi, Clara

AU - Poindexter, E. Christine

AU - Grignani, Francesco

AU - Pandolfi, Pier Paolo

AU - Lo Coco, Francesco

AU - Avvisati, Giuseppe

AU - Pelicci, Pier Giuseppe

AU - Jetten, Anton M.

PY - 1992/7/1

Y1 - 1992/7/1

N2 - The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RARα locus. The resulting chimeric gene encodes for a putative PML-RARα fusion protein. PML is a putative transcriptional factor and RARα is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RARα protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RARα. The introduction of the expression vector PSG5/PML-RARα into COS-1 cells led to high levels of expression of the PML-RARα fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RARα receptor. The PML-RARα fusion protein, but not the RARα, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RARα product was also found as a high molecular complex. The interaction of the PML-RARα with itself or with other nuclear proteins may be important in understanding the role of the PML-RARα fusion protein in promyelocytic leukemogenesis.

AB - The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RARα locus. The resulting chimeric gene encodes for a putative PML-RARα fusion protein. PML is a putative transcriptional factor and RARα is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RARα protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RARα. The introduction of the expression vector PSG5/PML-RARα into COS-1 cells led to high levels of expression of the PML-RARα fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RARα receptor. The PML-RARα fusion protein, but not the RARα, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RARα product was also found as a high molecular complex. The interaction of the PML-RARα with itself or with other nuclear proteins may be important in understanding the role of the PML-RARα fusion protein in promyelocytic leukemogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0026627897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026627897&partnerID=8YFLogxK

M3 - Article

C2 - 1319828

AN - SCOPUS:0026627897

VL - 52

SP - 3687

EP - 3692

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 13

ER -