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Nucleolin is a protein that in humans is encoded by the NCLgene.[5][6]
Gene
The human NCL gene is located on chromosome 2 and consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20.[7]
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).[8]
Clinical significance
Midkine and pleiotrophin bind to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.[9][10]
Nucleolin at the cell surface is the receptor for the Respiratory Syncytial Virus (RSV) fusion protein.[11] Interference with the nucleolin - RSV fusion protein interaction has been shown to be therapeutic against RSV infection in cell cultures and animal models.[12][13][14][15]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Srivastava M, McBride OW, Fleming PJ, Pollard HB, Burns AL (Sep 1990). "Genomic organization and chromosomal localization of the human nucleolin gene". The Journal of Biological Chemistry. 265 (25): 14922–31. PMID2394707.
^Erard MS, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F (Aug 1988). "A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1". European Journal of Biochemistry / FEBS. 175 (3): 525–30. doi:10.1111/j.1432-1033.1988.tb14224.x. PMID3409881.
^Mastrangelo P, Hegele RG (Nov 2012). "The RSV fusion receptor: not what everyone expected it to be". Microbes and Infection / Institut Pasteur. 14 (13): 1205–10. doi:10.1016/j.micinf.2012.07.015. PMID22884716.
^Shakeri A, Mastrangelo P, Griffin JK, Moraes TJ, Hegele RG (Nov 2014). "Respiratory syncytial virus receptor expression in the mouse and viral tropism". Histology and Histopathology. 30 (30): 401–411. doi:10.14670/HH-30.401. PMID25374027.
^Li D, Dobrowolska G, Krebs EG (Jun 1996). "The physical association of casein kinase 2 with nucleolin". The Journal of Biological Chemistry. 271 (26): 15662–8. doi:10.1074/jbc.271.26.15662. PMID8663258.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Dubois T, Zemlickova E, Howell S, Aitken A (Feb 2003). "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin". Biochemical and Biophysical Research Communications. 301 (2): 502–8. doi:10.1016/s0006-291x(02)03010-3. PMID12565890.
^Morimoto H, Okamura H, Haneji T (Sep 2002). "Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells". The Journal of Histochemistry and Cytochemistry. 50 (9): 1187–93. doi:10.1177/002215540205000905. PMID12185196.
^Fouraux MA, Bouvet P, Verkaart S, van Venrooij WJ, Pruijn GJ (Jul 2002). "Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes". Journal of Molecular Biology. 320 (3): 475–88. doi:10.1016/s0022-2836(02)00518-1. PMID12096904.
^Bharti AK, Olson MO, Kufe DW, Rubin EH (Jan 1996). "Identification of a nucleolin binding site in human topoisomerase I". The Journal of Biological Chemistry. 271 (4): 1993–7. doi:10.1074/jbc.271.4.1993. PMID8567649.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (Dec 2004). "Nucleolin interacts with telomerase". The Journal of Biological Chemistry. 279 (49): 51508–15. doi:10.1074/jbc.M407643200. PMID15371412.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Further reading
Tuteja R, Tuteja N (1999). "Nucleolin: a multifunctional major nucleolar phosphoprotein". Critical Reviews in Biochemistry and Molecular Biology. 33 (6): 407–36. doi:10.1080/10409239891204260. PMID9918513.
Pasternack MS, Bleier KJ, McInerney TN (Aug 1991). "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. PMID1860869.
Srivastava M, Fleming PJ, Pollard HB, Burns AL (Jun 1989). "Cloning and sequencing of the human nucleolin cDNA". FEBS Letters. 250 (1): 99–105. doi:10.1016/0014-5793(89)80692-1. PMID2737305.
Tuteja N, Huang NW, Skopac D, Tuteja R, Hrvatic S, Zhang J, Pongor S, Joseph G, Faucher C, Amalric F (Jul 1995). "Human DNA helicase IV is nucleolin, an RNA helicase modulated by phosphorylation". Gene. 160 (2): 143–8. doi:10.1016/0378-1119(95)00207-M. PMID7642087.
Jordan P, Heid H, Kinzel V, Kübler D (Dec 1994). "Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins". Biochemistry. 33 (49): 14696–706. doi:10.1021/bi00253a007. PMID7993898.
Eggert M, Möws CC, Tripier D, Arnold R, Michel J, Nickel J, Schmidt S, Beato M, Renkawitz R (Dec 1995). "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. doi:10.1074/jbc.270.51.30755. PMID8530516.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Bharti AK, Olson MO, Kufe DW, Rubin EH (Jan 1996). "Identification of a nucleolin binding site in human topoisomerase I". The Journal of Biological Chemistry. 271 (4): 1993–7. doi:10.1074/jbc.271.4.1993. PMID8567649.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Li YP, Busch RK, Valdez BC, Busch H (Apr 1996). "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". European Journal of Biochemistry / FEBS. 237 (1): 153–8. doi:10.1111/j.1432-1033.1996.0153n.x. PMID8620867.
Li D, Dobrowolska G, Krebs EG (Jun 1996). "The physical association of casein kinase 2 with nucleolin". The Journal of Biological Chemistry. 271 (26): 15662–8. doi:10.1074/jbc.271.26.15662. PMID8663258.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Zhou G, Seibenhener ML, Wooten MW (Dec 1997). "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. doi:10.1074/jbc.272.49.31130. PMID9388266.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Borggrefe T, Wabl M, Akhmedov AT, Jessberger R (Jul 1998). "A B-cell-specific DNA recombination complex". The Journal of Biological Chemistry. 273 (27): 17025–35. doi:10.1074/jbc.273.27.17025. PMID9642267.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Larrucea S, González-Rubio C, Cambronero R, Ballou B, Bonay P, López-Granados E, Bouvet P, Fontán G, Fresno M, López-Trascasa M (Nov 1998). "Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement". The Journal of Biological Chemistry. 273 (48): 31718–25. doi:10.1074/jbc.273.48.31718. PMID9822633.{{cite journal}}: CS1 maint: unflagged free DOI (link)
