RARA Gene
The RARA gene, also known as NR1B1, is a protein coding gene located on chromosome 17 that provides the instructions required to make transcription factor Retinoic Acid Receptor Alpha (or RARα).[1]
Interactions and roles[edit]
The RARα protein interacts with Vitamin A-derived retinoic acid to control the transcription of genes required for many processes involved in early embryonic development including neural differentiation, organogenesis, cardiogenesis, and limb development.[2][3][4] It also plays an important role in the development of the immune system by inducing T-regulatory cells, promoting tolerance, and controlling the differentiation of immature immune cells in the bone marrow called promyelocytes into mature white blood cells.[5]
Defects[edit]
RARA’s role in the developing immune system leaves it subject to possible defects, the most common of which is a condition known as Acute Promyeloid Leukemia (APL) caused by a somatic mutation described by the fusion of RARA and the PML gene located on chromosome 15.[1] This fusion results in the formation of the protein complex PML-RARα Under normal circumstances, PML produces a tumor suppressing protein that works by inhibiting uncontrolled rapid cell growth. When the two proteins fuse together, their normal functions are hindered, resulting in the accumulation of promyelocytes in the bone marrow unable to differentiate past this immature phase.[1] This fusion makes up for the cause of 98% of APL cases, with some other rare mutations and fusions making up the other 2%.[6] Current treatment approaches include all-trans-retinoic acid (ATRA) which works by targeting and degrading the PML-RARα protein complex, in addition to chemotherapy and platelet transfusions.[7]
References[edit]
- ^ a b c Liquori, Alessandro; Ibañez, Mariam; Sargas, Claudia; Sanz, Miguel Ángel; Barragán, Eva; Cervera, José (8 March 2020). "Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene". Cancers. 12 (3): 624. doi:10.3390/cancers12030624. PMC 7139833. PMID 32182684.
- ^ Janesick, Amanda; Wu, Stephanie Cherie; Blumberg, Bruce (April 2015). "Retinoic acid signaling and neuronal differentiation". Cellular and Molecular Life Sciences. 72 (8): 1559–1576. doi:10.1007/s00018-014-1815-9. PMID 25558812. S2CID 253591169.
- ^ Duester, Gregg (September 2008). "Retinoic Acid Synthesis and Signaling during Early Organogenesis". Cell. 134 (6): 921–931. doi:10.1016/j.cell.2008.09.002. PMC 2632951. PMID 18805086.
- ^ Kam, Richard Kin Ting; Deng, Yi; Chen, Yonglong; Zhao, Hui (22 March 2012). "Retinoic acid synthesis and functions in early embryonic development". Cell & Bioscience. 2 (1): 11. doi:10.1186/2045-3701-2-11. PMC 3325842. PMID 22439772.
- ^ Mora, J. Rodrigo; Iwata, Makoto; von Andrian, Ulrich H. (September 2008). "Vitamin effects on the immune system: vitamins A and D take centre stage". Nature Reviews Immunology. 8 (9): 685–698. doi:10.1038/nri2378. PMC 2906676. PMID 19172691.
- ^ Huang, Hai; Cao, Kaiming; Kong, Yaqiong; Yuan, Siming; Liu, Hongke; Wang, Yucai; Liu, Yangzhong (14 November 2019). "A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells". Chemical Science. 10 (42): 9721–9728. doi:10.1039/c9sc03110c. PMC 6993625. PMID 32055340.
- ^ Stahl, Maximilian; Tallman, Martin S. (10 November 2019). "Acute promyelocytic leukemia (APL): remaining challenges towards a cure for all". Leukemia & Lymphoma. 60 (13): 3107–3115. doi:10.1080/10428194.2019.1613540. PMC 7479633. PMID 31842650.
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