Retinoids (RA) are metabolites of vitamin A (retinol) that are important signaling molecules during vertebrate development and tissue differentiation. RAs activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) nuclear transcription factor families. Most retinoid forms activate RAR family members, whereas RXR family members are activated by 9-cis-RA only. RAR family members, which include RARα, RARβ and RARγ, have a high affinity for all transretinoic acids and belong to the same class of nuclear transcription factors as thyroid hormone receptors, vitamin D3 receptor and ecdysone receptor. RAR isoforms are expressed in distinct patterns throughout development and in the mature organism. The human RARα gene maps to chromosome 17 and is implicated in the chromosomal translocation associated with acute promyelocytic leukemia (APL-M3). Specifically, the RARα gene is fused with the promyelocytic leukemia (PML) gene, which encodes the fusion protein PML/RARα. The PML/RARα fusion protein inhibits PML-dependent apoptotic pathways and halts myeloid differentiation at the promyelocytic stage.
