Biology:Nucleolin
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Short description: Protein
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Nucleolin is a protein that in humans is encoded by the NCL gene.[1][2]
Gene
The human NCL gene is located on chromosome 2 and consists of 14 exons with 13 introns and spans approximately 11kb. Intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20.[3]
Function
Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats.
Nucleolin is also able to act as a transcriptional coactivator with Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII).[4]
Clinical significance
Midkine and pleiotrophin bind to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.[5][6]
Nucleolin at the cell surface is the receptor for the respiratory syncytial virus (RSV) fusion protein.[7] Interference with the nucleolin–RSV fusion protein interaction has been shown to be therapeutic against RSV infection in cell cultures and animal models.[8][9][10][11]
Interactions
Nucleolin has been shown to interact with:
- MTDH,[12]
- CSNK2A2,[13]
- Centaurin, alpha 1,[14]
- HuR,[15]
- NPM1,[16]
- P53,[17]
- PPP1CB,[18]
- S100A11,[19]
- Sjogren syndrome antigen B,[20]
- TOP1,[21][22] and
- Telomerase reverse transcriptase.[23]
References
- ↑ "Genomic organization and chromosomal localization of the human nucleolin gene". The Journal of Biological Chemistry 265 (25): 14922–31. Sep 1990. doi:10.1016/S0021-9258(18)77205-0. PMID 2394707.
- ↑ "A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1". European Journal of Biochemistry 175 (3): 525–30. Aug 1988. doi:10.1111/j.1432-1033.1988.tb14224.x. PMID 3409881.
- ↑ "Entrez Gene: NCL nucleolin". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4691.
- ↑ "Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells". PLOS ONE 7 (5): e38278. May 2012. doi:10.1371/journal.pone.0038278. PMID 22693611. Bibcode: 2012PLoSO...738278L.
- ↑ "The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor". The Journal of Biological Chemistry 277 (40): 37492–502. Oct 2002. doi:10.1074/jbc.M201194200. PMID 12147681.
- ↑ "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". The FEBS Journal 272 (18): 4646–59. Sep 2005. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786.
- ↑ "Identification of nucleolin as a cellular receptor for human respiratory syncytial virus". Nature Medicine 17 (9): 1132–5. Sep 2011. doi:10.1038/nm.2444. PMID 21841784.
- ↑ "The Susceptibilities of Respiratory Syncytial Virus to Nucleolin Receptor Blocking and Antibody Neutralization are Dependent upon the Method of Virus Purification". Viruses 9 (8): 207. Aug 2017. doi:10.3390/v9080207. PMID 28771197.
- ↑ "The RSV fusion receptor: not what everyone expected it to be". Microbes and Infection / Institut Pasteur 14 (13): 1205–10. Nov 2012. doi:10.1016/j.micinf.2012.07.015. PMID 22884716.
- ↑ "RSV fusion: time for a new model". Viruses 5 (3): 873–85. Mar 2013. doi:10.3390/v5030873. PMID 23518574.
- ↑ "Respiratory syncytial virus receptor expression in the mouse and viral tropism". Histology and Histopathology 30 (30): 401–411. Nov 2014. doi:10.14670/HH-30.401. PMID 25374027.
- ↑ "Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling.". Cancers 13 (11): 2842. Jun 2021. doi:10.3390/cancers13112842. PMID 34200450.
- ↑ "The physical association of casein kinase 2 with nucleolin". The Journal of Biological Chemistry 271 (26): 15662–8. Jun 1996. doi:10.1074/jbc.271.26.15662. PMID 8663258.
- ↑ "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin". Biochemical and Biophysical Research Communications 301 (2): 502–8. Feb 2003. doi:10.1016/s0006-291x(02)03010-3. PMID 12565890.
- ↑ "Competitive regulation of nucleolin expression by HuR and miR-494". Molecular and Cellular Biology 31 (20): 4219–31. Oct 2011. doi:10.1128/MCB.05955-11. PMID 21859890.
- ↑ "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". European Journal of Biochemistry 237 (1): 153–8. Apr 1996. doi:10.1111/j.1432-1033.1996.0153n.x. PMID 8620867.
- ↑ "Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation". Molecular and Cellular Biology 22 (16): 6014–22. Aug 2002. doi:10.1128/mcb.22.16.6014-6022.2002. PMID 12138209.
- ↑ "Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells". The Journal of Histochemistry and Cytochemistry 50 (9): 1187–93. Sep 2002. doi:10.1177/002215540205000905. PMID 12185196.
- ↑ "S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes". The Journal of Cell Biology 163 (4): 825–35. Nov 2003. doi:10.1083/jcb.200304017. PMID 14623863.
- ↑ "Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes". Journal of Molecular Biology 320 (3): 475–88. Jul 2002. doi:10.1016/s0022-2836(02)00518-1. PMID 12096904.
- ↑ "Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen". Nucleic Acids Research 26 (7): 1841–7. Apr 1998. doi:10.1093/nar/26.7.1841. PMID 9512561.
- ↑ "Identification of a nucleolin binding site in human topoisomerase I". The Journal of Biological Chemistry 271 (4): 1993–7. Jan 1996. doi:10.1074/jbc.271.4.1993. PMID 8567649.
- ↑ "Nucleolin interacts with telomerase". The Journal of Biological Chemistry 279 (49): 51508–15. Dec 2004. doi:10.1074/jbc.M407643200. PMID 15371412.
Further reading
- "Nucleolin: a multifunctional major nucleolar phosphoprotein". Critical Reviews in Biochemistry and Molecular Biology 33 (6): 407–36. 1999. doi:10.1080/10409239891204260. PMID 9918513.
- "Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro". The Journal of Biological Chemistry 266 (22): 14703–8. Aug 1991. doi:10.1016/S0021-9258(18)98743-0. PMID 1860869.
- "Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase". Molecular and Cellular Biology 10 (7): 3607–18. Jul 1990. doi:10.1128/MCB.10.7.3607. PMID 2192260.
- "Cloning and sequencing of the human nucleolin cDNA". FEBS Letters 250 (1): 99–105. Jun 1989. doi:10.1016/0014-5793(89)80692-1. PMID 2737305.
- "Human DNA helicase IV is nucleolin, an RNA helicase modulated by phosphorylation". Gene 160 (2): 143–8. Jul 1995. doi:10.1016/0378-1119(95)00207-M. PMID 7642087.
- "Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins". Biochemistry 33 (49): 14696–706. Dec 1994. doi:10.1021/bi00253a007. PMID 7993898.
- "U20, a novel small nucleolar RNA, is encoded in an intron of the nucleolin gene in mammals". Molecular and Cellular Biology 14 (9): 5766–76. Sep 1994. doi:10.1128/mcb.14.9.5766. PMID 8065311.
- "Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n". Molecular and Cellular Biology 13 (7): 4301–10. Jul 1993. doi:10.1128/MCB.13.7.4301. PMID 8321232.
- "A fraction enriched in a novel glucocorticoid receptor-interacting protein stimulates receptor-dependent transcription in vitro". The Journal of Biological Chemistry 270 (51): 30755–9. Dec 1995. doi:10.1074/jbc.270.51.30755. PMID 8530516.
- "Identification of a nucleolin binding site in human topoisomerase I". The Journal of Biological Chemistry 271 (4): 1993–7. Jan 1996. doi:10.1074/jbc.271.4.1993. PMID 8567649.
- "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". European Journal of Biochemistry 237 (1): 153–8. Apr 1996. doi:10.1111/j.1432-1033.1996.0153n.x. PMID 8620867.
- "The physical association of casein kinase 2 with nucleolin". The Journal of Biological Chemistry 271 (26): 15662–8. Jun 1996. doi:10.1074/jbc.271.26.15662. PMID 8663258.
- "Nucleolin is a protein kinase C-zeta substrate. Connection between cell surface signaling and nucleus in PC12 cells". The Journal of Biological Chemistry 272 (49): 31130–7. Dec 1997. doi:10.1074/jbc.272.49.31130. PMID 9388266.
- "Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen". Nucleic Acids Research 26 (7): 1841–7. Apr 1998. doi:10.1093/nar/26.7.1841. PMID 9512561.
- "A B-cell-specific DNA recombination complex". The Journal of Biological Chemistry 273 (27): 17025–35. Jul 1998. doi:10.1074/jbc.273.27.17025. PMID 9642267.
- "Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement". The Journal of Biological Chemistry 273 (48): 31718–25. Nov 1998. doi:10.1074/jbc.273.48.31718. PMID 9822633.
- "A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription". The EMBO Journal 18 (13): 3688–701. Jul 1999. doi:10.1093/emboj/18.13.3688. PMID 10393184.
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