Retinoic acid receptor

Retinoic acid receptor (RAR) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid. There are three retinoic acid receptors (RAR), RAR-alpha, RAR-beta, and RAR-gamma, each of which is encoded by a separate gene. All three receptors are members of the thyroid-steroid hormone receptor superfamily of endogenous nuclear receptors.

Function

Retinoic acid receptors mediate the biological effects of retinoic acid, which is involved in cell growth and differentiation. They do this by controlling gene expression. When there is no retinoic acid present, the receptors repress gene expression. When retinoic acid is present, the receptors act as transcription factors, binding to DNA and regulating the transcription of specific genes.

Structure

Each RAR consists of several domains, including a DNA-binding domain and a ligand-binding domain. The DNA-binding domain recognizes and binds to specific sequences of DNA called retinoic acid response elements (RAREs). The ligand-binding domain binds to retinoic acid.

Role in Disease

Mutations in the retinoic acid receptor genes can lead to various diseases. For example, mutations in the RAR-alpha gene have been associated with acute promyelocytic leukemia (APL). In this disease, the RAR-alpha gene on chromosome 17 is translocated to a region on chromosome 15. This results in a fusion protein that disrupts the normal function of the retinoic acid receptor, leading to the development of leukemia.

Therapeutic Use

Retinoic acid and its derivatives are used in the treatment of various diseases, including acne, psoriasis, and certain types of cancer. For example, all-trans retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia. ATRA binds to the abnormal retinoic acid receptor in APL cells, causing them to mature and die.

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