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The self-association coiled-coil domain of PML is sufficient for the oncogenic conversion of the retinoic acid receptor (RAR) alpha.
- Source :
- Leukemia (08876924); May2011, Vol. 25 Issue 5, p814-820, 7p, 1 Diagram, 4 Graphs
- Publication Year :
- 2011
-
Abstract
- In acute promyelocytic leukemia (APL) the retinoic acid receptor alpha (RARα) becomes an oncogene through the fusion with several partners, mostly with promyelocytic leukemia protein (PML), all of which have in common the presence of a self-association domain. The new fusion proteins, therefore, differently from the wild-type RARα, which forms only heterodimers with retinoic X receptor alpha, are also able to homo-oligomerize. The presence of such a domain has been suggested to be crucial for the leukemogenic potential of the chimeric proteins found in APL blasts. Whether or not any self-association domain is sufficient to bestow a leukemogenic activity on RARα is still under investigation. In this work, we address this question using two different X-RARα chimeras, where X represents the coiled-coil domain of PML (CC-RARα) or the oligomerization portion of the yeast transcription factor GCN4 (GCN4-RARα). We demonstrate that in vitro both proteins have transforming potential, and recapitulate the main PML-RARα biological properties, but CC-RARα is uniquely able to disrupt PML nuclear bodies. Indeed, in vivo only the CC-RARα chimera induces efficiently APL in a murine transplantation model. Thus, the PML CC domain represents the minimal structural determinant indispensable to transform RARα into an oncogenic protein. [ABSTRACT FROM AUTHOR]
- Subjects :
- LEUKEMIA
ONCOGENES
TRETINOIN
IMMUNOBLOTTING
GEL permeation chromatography
ANIMAL experimentation
BIOCHEMISTRY
CELL receptors
CHROMATOGRAPHIC analysis
COMPARATIVE studies
FLUORESCENT antibody technique
HEMATOPOIETIC stem cells
IMMUNOPHENOTYPING
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
MICE
POLYMERASE chain reaction
PROTEINS
RECOMBINANT proteins
RESEARCH
RNA
TRANSCRIPTION factors
WESTERN immunoblotting
EVALUATION research
NUCLEAR proteins
REVERSE transcriptase polymerase chain reaction
ACUTE promyelocytic leukemia
NEOPLASTIC cell transformation
PRECIPITIN tests
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 25
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 60513810
- Full Text :
- https://doi.org/10.1038/leu.2011.18