Fig. 2.
Fusion proteins in acute promyelocytic leukemia. (A) indicates the unliganded interactions of the RXR/RAR heterodimer with an N-CoR/Sin3/HDAC1 complex. Upon binding retinoid acid, the RXR/RAR heterodimer releases the corepressor complex and binds a coactivator complex with histone acetylase activity. (B) indicates the analogous interactions of the RXR/PML-RAR heterodimer with the corepressor complex. Release of the corepressor complex occurs only in the presence of pharmacological levels of retinoic acid. (C) depicts the ligand-independent binding of the corepressor complex to PLZF-RAR. (It has been proposed, but not yet been formally demonstrated, that liganded RXR/PLZF-RAR binds both coactivator and corepressor complexes.) Chromatin remodeling occurs only in the presence of both RA and an HDAC inhibitor.