Biology:KDM5A
 Generic protein structure example |
Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.[1][2]
Function
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein which regulates cell proliferation. It was formerly known as Retinoblastoma Binding Protein 2 (RBP2). This protein also interacts with rhombotin-2 which functions distinctly in erythropoiesis and in T-cell leukemogenesis. Rhombotin-2 is thought to either directly affect the activity of the encoded protein or may indirectly modulate the functions of the retinoblastoma protein by binding to this protein. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[2]
The Drosophila homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc.[3] It was recently renamed to Lysine Demethylase 5 (KDM5).
Enzymatically can be designated as a trimethyllysine dioxygenase, which is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily (EC 1.14.11.8).
Interactions
JARID1A has been shown to interact with Estrogen receptor alpha,[4] LMO2[5] and Retinoblastoma protein.[4][6]
JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.[7][8]
Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells.[9]
References
- ↑ "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product". Nature 352 (6332): 251–4. Jul 1991. doi:10.1038/352251a0. PMID 1857421. Bibcode: 1991Natur.352..251D.
- ↑ 2.0 2.1 "Entrez Gene: JARID1A jumonji, AT rich interactive domain 1A". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5927.
- ↑ "The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth". Genes & Development 21 (5): 537–51. Mar 2007. doi:10.1101/gad.1523007. PMID 17311883.
- ↑ 4.0 4.1 "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". The Journal of Biological Chemistry 276 (30): 28402–12. Jul 2001. doi:10.1074/jbc.M100313200. PMID 11358960.
- ↑ "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene 14 (13): 1531–9. Apr 1997. doi:10.1038/sj.onc.1200988. PMID 9129143.
- ↑ "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein". Molecular and Cellular Biology 14 (11): 7256–64. Nov 1994. doi:10.1128/mcb.14.11.7256. PMID 7935440.
- ↑ "Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock". Science 333 (6051): 1881–5. 2011. doi:10.1126/science.1206022. PMID 21960634. Bibcode: 2011Sci...333.1881D.
- ↑ "A molecular mechanism for circadian clock negative feedback". Science 332 (6036): 1436–9. 2011. doi:10.1126/science.1196766. PMID 21680841. Bibcode: 2011Sci...332.1436D.
- ↑ "Inhibition of osteogenic differentiation of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription". Stem Cells 29 (7): 1112–25. 2011. doi:10.1002/stem.663. PMID 21604327.
Further reading
- "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein". Molecular and Cellular Biology 14 (11): 7256–64. Nov 1994. doi:10.1128/mcb.14.11.7256. PMID 7935440.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. Jan 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Characterization of the retinoblastoma binding proteins RBP1 and RBP2". Oncogene 8 (11): 3149–56. Nov 1993. PMID 8414517.
- "Isolation and regional assignment of human chromosome 12p cDNAs". Genomics 29 (1): 44–52. Sep 1995. doi:10.1006/geno.1995.1213. PMID 8530100.
- "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. Apr 1996. doi:10.1006/abio.1996.0138. PMID 8619474.
- "Generation and analysis of 280,000 human expressed sequence tags". Genome Research 6 (9): 807–28. Sep 1996. doi:10.1101/gr.6.9.807. PMID 8889549.
- "Large-scale concatenation cDNA sequencing". Genome Research 7 (4): 353–8. Apr 1997. doi:10.1101/gr.7.4.353. PMID 9110174.
- "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene 14 (13): 1531–9. Apr 1997. doi:10.1038/sj.onc.1200988. PMID 9129143.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. Oct 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". The Journal of Biological Chemistry 276 (30): 28402–12. Jul 2001. doi:10.1074/jbc.M100313200. PMID 11358960.
- "A yeast four-hybrid system identifies Cdk-activating kinase as a regulator of the XPD helicase, a subunit of transcription factor IIH". The Journal of Biological Chemistry 276 (38): 35328–33. Sep 2001. doi:10.1074/jbc.M105570200. PMID 11445587.
- "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–5. Aug 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- "Binding of pRB to the PHD protein RBP2 promotes cellular differentiation". Molecular Cell 18 (6): 623–35. Jun 2005. doi:10.1016/j.molcel.2005.05.012. PMID 15949438.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. Jan 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Novel JARID1C/SMCX mutations in patients with X-linked mental retardation". Human Mutation 27 (4): 389. Apr 2006. doi:10.1002/humu.9420. PMID 16541399.
- "Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells". The Journal of Investigative Dermatology 126 (8): 1850–9. Aug 2006. doi:10.1038/sj.jid.5700324. PMID 16645588.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. Nov 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
External links
- JARID1A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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