Cancer Cell
Volume 9, Issue 2, February 2006, Pages 73-74
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Reconstructing a disease: What essential features of the retinoic acid receptor fusion oncoproteins generate acute promyelocytic leukemia?

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Acute promyelocytic leukemia (APL) is associated with rearrangement of the retinoic acid receptor α (RARα) gene leading to the formation of chimeric receptor proteins. In this issue of Cancer Cell, studies by Kwok et al. and Sternsdorf et al. indicate that the ability of the RARα oncoproteins to dimerize/multimerize is an essential feature required for the development of disease. Homodimerization allows RARα to bind to corepressors with increased affinity and the ability to bind to novel DNA sequences. However, artificial RARα dimers were weak oncogenes in vivo, indicating that the fusion partners confer additional properties to RARα to efficiently generate disease.

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