Fig. 1.

A) Structure of the promyelocytic leukemia (PML), retinoic acid receptor-α (RARα), and the PML-RARα fusion proteins. RING (R), B boxes (B), and coiled-coil (CC) domains in PML are indicated. The RARα DNA-binding domain (C) and hormone-binding domain (E) are shown. A, B, D, and F are other regulatory domains. PML-RARα retains the functional domains of both proteins, allowing dominant-negative activities on both PML and RARα. B) PML-RARα homodimers bind and repress RARα targets through enhanced recruitment of corepressors. Retinoic acid (RA) converts PML-RARα into an activator and restores differentiation, yielding clinical remission. HAT, histone acetyltransferase; HDAC, histone deacetylase (From de The et al, Nat Rev Cancer 2010;10:775-83).