Recently visited
Please sign in to see a list of articles you recently visited.
Recently updated
Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
Comments (post)
There are no comments posted here... Yet.

Two isoforms of RARA exists in human and mouse. RARA1 and RARA2 are generated by distinct promoters and alternative splicing.[1][2][3] RARA2 is inducible by retinoids through a retinoic acid response element in its promoter. [4] In estrogen receptor (ER)-positive breast cancer cells, RARA1 is inducible by estradiol (E2) through an estrogen response element in its promoter.[5][6]

  1. Petkovich M et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature, 330(6147):444-50. (PMID 2825025)
  2. Giguere V et al. Identification of a receptor for the morphogen retinoic acid. Nature, 330(6149):624-9. (PMID 2825036)
  3. Leroy P et al. Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid. EMBO J., 10(1):59-69. (PMID 1846598)
  1. Leroy P et al. Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element. Proc. Natl. Acad. Sci. U.S.A., 88(22):10138-42. (PMID 1658797)
  2. van der Leede BJ et al. Retinoic acid receptor alpha 1 isoform is induced by estradiol and confers retinoic acid sensitivity in human breast cancer cells. Mol. Cell. Endocrinol., 109(1):77-86. (PMID 7789618)
  3. Laganière J et al. Functional genomics identifies a mechanism for estrogen activation of the retinoic acid receptor alpha1 gene in breast cancer cells. Mol. Endocrinol., 19(6):1584-92. (PMID 15831516)
Covalent modifications

The transcriptional activity of RARA is modulated by modifications such as phosphorylation, ubiquitination, sumoylation and methylation. These post-translational modifications influence the cellular localization of the receptor, its heterodimerization with RXRs, DNA binding and its degradation.[1]

RA induces RAR phosphorylation on serine residues in the ligand binding domain and in the N-terminal region. In RARa, Ser 369 is phosphorylated by MSK1, facilitating recruitment of cyclin H to the ligand binding domain, and resulting in increased phosphorylation of residue 77 by cyclin H-regulated cdk7.[1] In addition, kinases activated by other signaling pathways can also phosphorylate RARs at other sites. For instance, PKC-mediated phosphorylation of RARs in the DBD results in abrogation of DNA binding and/or nuclear export.[1]

RARa can be tri-methylated at a Lys residue in the ligand binding domain and mono-methylated at another lysine located in the DNA binding domain.[2][3]

  1. Rochette-Egly C and Germain P. Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs). , 7:e005. (PMID 19471584)
  2. Huq MD et al. Lysine trimethylation of retinoic acid receptor-alpha: a novel means to regulate receptor function. Mol. Cell Proteomics, 6(4):677-88. (PMID 17205979)
  1. Huq MD et al. Modulation of retinoic acid receptor alpha activity by lysine methylation in the DNA binding domain. J. Proteome Res., 7(10):4538-45. (PMID 18781795)