Abstract
Retinoic acid receptors (RARs) are members of a much larger group of ligand-dependent transcription factors, the so-called nuclear receptors. In mammals, there are three distinct RAR subtypes: RAR, RAR and RAR.1 RARs share a high sequence homology, but show distinct transcriptional properties and expression pattern, suggesting similar but not necessarily overlapping functions. In haematopoietic differentiation, for example, the function of RAR is uniquely required to maintain the stem cell compartment, whereas RAR seems to work primarily at later stages, favouring differentiation.2 In acute promyelocytic leukaemia (APL), chromosomal translocations involve in 100% of cases the -subtype of the RAR gene (RAR), on chromosome 17. These translocations lead to the synthesis of chimeric proteins: in 95% of the cases, the translocation partner is the PML (promyelocytic leukaemia) gene on chromosome 15, leading to the formation of PML–RAR fusion gene.3 Both in vitro and in vivo studies have well defined the oncogenic roles of PML–RAR fusion protein in the pathogenesis of APL, acting as an altered RAR.4 In our previous work, we studied the transcriptional and biological properties of chimeric constructs where PML was fused to RAR or RAR to generate the PML–RAR and PML–RAR fusion proteins (which do not exist in nature). Both chimeric proteins demonstrated similar properties to PML–RAR in vitro.5 Here, we extended this analysis to determine directly whether PML–RAR (as a test case), like PML–RAR, is able to induce APL.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.