Disease relevance of NCL

• In addition, the data provide a possible explanation for the appearance of nucleolin and PARP-1 autoantibodies in some autoimmune diseases [1].
• The growth factor midkine (MK) is a cytokine that inhibits the attachment of human immunodeficiency virus particles by a mechanism similar to the nucleolin binding HB-19 pseudopeptide [2].
• Direct interaction between nucleolin and hepatitis C virus NS5B [3].
• The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells [4].
• METHODS: Terminal restriction fragment (TRF) was evaluated in 20 surgically resected hepatocellular carcinoma specimens (HCC), corresponding noncancerous liver tissue specimens (NCL), and in 10 liver tissue specimens with chronic liver diseases devoid of cancer (DOC) [5].

Psychiatry related information on NCL

• Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology [6].

High impact information on NCL

• We show that an element within D4Z4 specifically binds a multiprotein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin [7].
• Three classes of proteins were studied: first, wild-type and mutant forms of nucleolin, one of the first shuttling proteins identified; second, artificial nuclear reporter proteins derived from cytoplasmic pyruvate kinase; and third, wild-type and mutant lamins differing in their abilities to be incorporated into the lamina [8].
• We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to the JRE [9].
• The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells [10].
• Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18(+) cervical cancer cell growth [10].

Chemical compound and disease context of NCL

• Consequently, equilibrium density fractionation of extracts from infected cells revealed that HIV proteins and nucleolin copurify with Triton X-100-resistant GEM-associated proteins [11].
• Taken together, our results suggest that nucleolin, PHAP II, and PHAP I appear to be functional as potential receptors in the HIV binding process by virtue of their capacity to interact with the V3 loop of gp120 [12].
• TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid [13].
• Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression [14].

Biological context of NCL

• We recently discovered that heat shock causes nucleolin to relocalize from the nucleolus to the nucleoplasm, whereupon it binds replication protein A and inhibits DNA replication initiation [15].
• On the other hand, down-regulation of nucleolin by RNA interference did not affect aprataxin protein levels but abolished its nucleolar localization suggesting that the interaction with nucleolin is involved in its nucleolar targeting [16].
• These data indicate a novel p53-dependent mechanism in which cell stress mobilizes nucleolin for transient replication inhibition and DNA repair [15].
• Nucleolin relocalization and complex formation in vivo were independent of p53 transactivation but required the p53 C-terminal regulatory domain [15].
• Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin [1].

Anatomical context of NCL

• Nucleolin functions in ribosome biogenesis and contains an acidic N terminus that binds nuclear localization sequences [17].
• Additionally, nucleolin levels were dramatically decreased in extracts containing the cytoplasm and plasma membrane [1].
• Here, we report our findings that UV irradiation or camptothecin treatment of U937 cells induced apoptosis and caused a significant change in the levels and localization of nucleolin within the nucleus [1].
• Both proteins were co-immunoprecipitated from HeLa cell nuclear extract by either monoclonal anti-C23 or monoclonal anti-B23 [18].
• These results show that cell surface nucleolin is a specific marker of angiogenic endothelial cells within the vasculature [19].

Associations of NCL with chemical compounds

• These alterations could be abrogated by pre-incubation with an inhibitor of PARP-1 (3-aminobenzamide), and our data support a potential role for nucleolin in removing cleaved PARP-1 from dying cells [1].
• Antibodies and cell surface biotin labeling revealed nucleolin at the surface of actively growing cells, and these cells bound and internalized fluorescein-conjugated F3 peptide, transporting it into the nucleus [19].
• This binding was inhibited by anti-nucleolin antibody, by polylactosamine-containing oligosaccharides, and by anti-CD43 antibody [20].
• Nucleolin-transfected HEK293 cells expressed nucleolin on the cell surface and bound the early apoptotic cells but not phosphatidylserine-exposing late apoptotic cells [20].
• Scanning clustered alanine substitution mutants library of NS5B revealed two sites on NS5B that binds nucleolin [3].

Physical interactions of NCL

• Nucleolin interacts with telomerase [21].
• We suggest a biological role of nucleolin in binding of GR in the nucleolus [22].
• We identify nucleolin as one of the nuclear polypeptides that interact specifically with the A-Myb and c-Myb, but not B-Myb DNA-binding domains [23].
• The growth factor midkine (MK) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles [24].
• The target cell substrates of granzymes are unknown, but granzyme A binding and cleavage of the nuclear shuttle protein nucleolin in target cells demonstrates that granzymes may act on nuclear substrates [25].

Enzymatic interactions of NCL

• Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies [1].
• Moreover, as the pattern of staining does not vary using casein kinase II- and cdc2-phosphorylated nucleolin or dephosphorylated nucleolin, we conclude that the reduction of the silver ions is not linked to the phosphorylation state of the molecule [26].

Co-localisations of NCL

• Furthermore, nucleolin co-localized with p53 to these foci, suggesting that these foci were nucleolar structures [27].
• RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin [28].

Regulatory relationships of NCL

• Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell-surface-expressed nucleolin at distinct spots [2].
• Role of nucleolin in posttranscriptional control of MMP-9 expression [29].
• These properties of nucleolin were identical with those of the p95 previously described and induced by CR2 activation [30].
• Reduced phosphorylated nucleolin and retinoblastoma protein levels showed it also efficiently inhibited cellular CDK1 and CDK2 activity (IC(50) 50-100 and 200-500 nM, respectively) [31].
• Here we report that the nuclear protein nucleolin possesses a histone chaperone activity and that this factor greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and ACF [32].

Other interactions of NCL

• Here, we show that nucleolin, a major nucleolar phosphoprotein, interacts with telomerase and alters its subcellular localization [21].
• The protein-protein interaction between nucleolin and hTERT is critical for the nucleolar localization of hTERT [21].
• Identification of nucleolin as a glucocorticoid receptor interacting protein [22].
• In AOA1 cells lacking aprataxin, the stability of nucleolin was significantly reduced [16].
• In this study, we have examined apoptosis-induced alterations in two proteins, nucleolin and poly(ADP-ribose) polymerase-1 (PARP-1), in U937 leukemia cells [1].

Analytical, diagnostic and therapeutic context of NCL

• The interaction FJ-nucleolin was evidenced by Western blot and enzyme-linked immunosorbent assay [33].
• We used affinity chromatography with a topo I fusion protein to screen U-937 leukemic cell extracts and have identified nucleolin as a topo I-binding protein [34].
• A band with higher molecular mass (113 kDa) than the 105-kDa classical major nucleolin band was detected on SDS-PAGE gel that cross-reacted with specific anti-nucleolin antibodies and was identified as a nucleolin isoform by mass spectrometry [35].
• Then 4-micron sections were evaluated by immunohistochemistry, using the peroxidase method to determine the expression of p53 in Wilms' tumor cells by means of primary monoclonal antibody NCL-p53 from Novocastra [36].
• In vivo labeling with 32Pi and stimulation of PC12 cells with NGF followed by immunoprecipitation with anti-nucleolin antibody corroborated the in vitro approach documenting enhanced phosphorylation of nucleolin by NGF treatment [37].

References