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
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Nucleolin has been shown to interact with:
MTDH ,[ 16] CSNK2A2 ,[ 17] Centaurin, alpha 1 ,[ 18] HuR ,[ 19] NPM1 ,[ 20] P53 ,[ 21] PPP1CB ,[ 22] S100A11 ,[ 23] Sjögren syndrome antigen B ,[ 24] TOP1 ,[ 25] [ 26] Telomerase reverse transcriptase .[ 27]
^ a b c GRCh38: Ensembl release 89: ENSG00000115053 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026234 – Ensembl , May 2017^ "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. doi :10.1016/S0021-9258(18)77205-0 PMID 2394707 . ^ 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 . 175 (3): 525–30. doi :10.1111/j.1432-1033.1988.tb14224.x PMID 3409881 . ^ "Entrez Gene: NCL nucleolin" .^ Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, Klinge CM (May 2012). "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. Bibcode :2012PLoSO...738278L . doi :10.1371/journal.pone.0038278 PMC 3365040 PMID 22693611 . ^ Said EA, Krust B, Nisole S, Svab J, Briand JP, Hovanessian AG (Oct 2002). "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. doi :10.1074/jbc.M201194200 PMID 12147681 . S2CID 41621217 . ^ Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG (Sep 2005). "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin" . The FEBS Journal . 272 (18): 4646–59. doi :10.1111/j.1742-4658.2005.04870.x PMID 16156786 . S2CID 21153881 . ^ Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG (Sep 2011). "Identification of nucleolin as a cellular receptor for human respiratory syncytial virus". Nature Medicine . 17 (9): 1132–5. doi :10.1038/nm.2444 . PMID 21841784 . S2CID 205388029 . ^ Bilawchuk LM, Griffiths CD, Jensen LD, Elawar F, Marchant DJ (Aug 2017). "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. doi :10.3390/v9080207 PMC 5580464 PMID 28771197 . ^ 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 . PMID 22884716 . ^ Mastrangelo P, Hegele RG (Mar 2013). "RSV fusion: time for a new model" . Viruses . 5 (3): 873–85. doi :10.3390/v5030873 PMC 3705301 PMID 23518574 . ^ 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 . PMID 25374027 . ^ Lee, Seong-Jae, et al. (Jun 2021). "Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling" . Cancers . 13 (11): 2842. doi :10.3390/cancers13112842 PMC 8201222 PMID 34200450 . S2CID 235436955 . ^ 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 PMID 8663258 . S2CID 10750338 . ^ 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 . PMID 12565890 . ^ Tominaga K, Srikantan S, Lee EK, Subaran SS, Martindale JL, Abdelmohsen K, Gorospe M (Oct 2011). "Competitive regulation of nucleolin expression by HuR and miR-494" . Molecular and Cellular Biology . 31 (20): 4219–31. doi :10.1128/MCB.05955-11 . PMC 3187287 PMID 21859890 . ^ 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 . 237 (1): 153–8. doi :10.1111/j.1432-1033.1996.0153n.x PMID 8620867 . ^ Daniely Y, Dimitrova DD, Borowiec JA (Aug 2002). "Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation" . Molecular and Cellular Biology . 22 (16): 6014–22. doi :10.1128/mcb.22.16.6014-6022.2002 . PMC 133981 PMID 12138209 . ^ 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 PMID 12185196 . S2CID 24950287 . ^ Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, Yamada H, Namba M, Huh NH (Nov 2003). "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. doi :10.1083/jcb.200304017 . PMC 2173690 PMID 14623863 . ^ 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 . hdl :2066/121576 PMID 12096904 . ^ Haluska P, Saleem A, Edwards TK, Rubin EH (Apr 1998). "Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen" . Nucleic Acids Research . 26 (7): 1841–7. doi :10.1093/nar/26.7.1841 . PMC 147454 PMID 9512561 . ^ 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 PMID 8567649 . S2CID 25059254 . ^ 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 hdl :2297/15897 PMID 15371412 . S2CID 41394148 .
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