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Gene Review

NOP2  -  NOP2 nucleolar protein

Homo sapiens

Synonyms: NOL1, NOP120, NSUN1, Nucleolar protein 1, Nucleolar protein 2 homolog, ...
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Disease relevance of NOL1


High impact information on NOL1

  • Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120 [5].
  • AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised [5].
  • Surprisingly, PDGFR-induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho [5].
  • By affecting RhoA activation, p120 could modulate cadherin functions, including suppression of invasion, neurite extension and junction formation [6].
  • Overexpression of p120, but not an NH2-terminal deletion mutant deficient in kinesin binding, recruits endogenous kinesin to N-cadherin [7].

Biological context of NOL1


Anatomical context of NOL1

  • Expression patterns for ac-catenin, p120, and E-cadherin were similar to beta-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed [13].
  • The middle region of the antisense p120 RNA was found to be almost as inhibitory as the full length antisense construct but the 5' and 3' antisense portions did not affect NIH 3T3 cell proliferation [10].
  • These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton [14].
  • The human proliferation-associated nucleolar antigen p120 was localized to substructures within HeLa cell nucleoli by immunofluorescence and immunoelectron microscopy of cells whose nucleoli were segregated by drug treatment or extracted with nucleases [15].
  • Plakophilins are a subfamily of p120-related arm-repeat proteins that can be found in both desmosomes and the nucleus [16].

Associations of NOL1 with chemical compounds

  • The aim of the present study was to examine the expression and cellular localisation of alpha and beta-catenin, p120 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH) [13].
  • Drug-induced segregation of nucleoli by actinomycin D or dichlorobenzimidazole riboside, followed by immunoelectron microscopy, indicated that protein p120 was concentrated at the periphery of the granular region in segregated nucleoli [15].
  • Although p120 tyrosine phosphorylation is a leading candidate, the role of this modification in normal and Src-transformed cells remains unknown [17].
  • Changing all of these sites to phenylalanine resulted in a p120 mutant, p120-8F, that could not be efficiently phosphorylated by Src and failed to interact with SHP-1, a tyrosine phosphatase shown previously to interact selectively with tyrosine-phosphorylated p120 in cells stimulated with epidermal growth factor [17].
  • To demonstrate that cytoplasmic p120 localization was a consequence of the absence of E-CD, the endogenous E-CD was re-expressed in MDA-231 cells by 5-Aza-2'-deoxycytidine (5Aza) treatment [1].

Physical interactions of NOL1

  • Deletion analysis showed that amino acids 187-215 of protein B23 bound to protein p120 [18].
  • Transfection experiments in CHO cells showed that p120 could bind to a VE-cadherin cytoplasmic region different from that responsible for beta-catenin binding, and PV stabilized this association [19].
  • These results support a model in which the VE-cadherin tail mediates interactions with clathrin-dependent endocytic machinery, and this endocytic processing is inhibited by p120 binding to the cadherin tail [20].
  • Overall, the results indicate that E- and N-cadherin assemble stoichiometrically different complexes with p120 in the same cells [21].
  • Alternatively, p120 may stabilize cell junctions or regulate membrane trafficking machinery through interactions with small GTPases such as Rho A, Rac and Cdc42 [22].

Regulatory relationships of NOL1

  • The human nucleolar p120 protein is a proliferation-associated antigen which is expressed in G1 and peaks during the early S phase of the cell cycle [10].
  • Several observations suggest that p120 can both positively and negatively regulate cadherin adhesiveness depending on signals that so far remain unidentified [17].

Other interactions of NOL1


Analytical, diagnostic and therapeutic context of NOL1


  1. Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. Sarrió, D., Pérez-Mies, B., Hardisson, D., Moreno-Bueno, G., Suárez, A., Cano, A., Martín-Pérez, J., Gamallo, C., Palacios, J. Oncogene (2004) [Pubmed]
  2. Role of E-cadherin, alpha-, beta-, and gamma-catenins, and p120 (cell adhesion molecules) in prolactinoma behavior. Qian, Z.R., Li, C.C., Yamasaki, H., Mizusawa, N., Yoshimoto, K., Yamada, S., Tashiro, T., Horiguchi, H., Wakatsuki, S., Hirokawa, M., Sano, T. Mod. Pathol. (2002) [Pubmed]
  3. Phosphorylation of gastrin-17 by epidermal growth factor-stimulated tyrosine kinase. Baldwin, G.S., Knesel, J., Monckton, J.M. Nature (1983) [Pubmed]
  4. Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma. Sato, G., Saijo, Y., Uchiyama, B., Kumano, N., Sugawara, S., Fujimura, S., Sato, M., Sagawa, M., Ohkuda, K., Koike, K., Minami, Y., Satoh, K., Nukiwa, T. J. Clin. Oncol. (1999) [Pubmed]
  5. p120-Catenin and p190RhoGAP Regulate Cell-Cell Adhesion by Coordinating Antagonism between Rac and Rho. Wildenberg, G.A., Dohn, M.R., Carnahan, R.H., Davis, M.A., Lobdell, N.A., Settleman, J., Reynolds, A.B. Cell (2006) [Pubmed]
  6. Inhibition of RhoA by p120 catenin. Anastasiadis, P.Z., Moon, S.Y., Thoreson, M.A., Mariner, D.J., Crawford, H.C., Zheng, Y., Reynolds, A.B. Nat. Cell Biol. (2000) [Pubmed]
  7. p120 catenin associates with kinesin and facilitates the transport of cadherin-catenin complexes to intercellular junctions. Chen, X., Kojima, S., Borisy, G.G., Green, K.J. J. Cell Biol. (2003) [Pubmed]
  8. Assignment of the gene for the human proliferating cell nucleolar protein P120 (NOL1) to chromosome 12p13 by fluorescence in situ hybridization and polymerase chain reaction with somatic cell hybrids. Baens, M., Chaffanet, M., Aerssens, J., Cassiman, J.J., Marynen, P. Genomics (1994) [Pubmed]
  9. The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with nucleolar protein p120. Ren, Y., Busch, R.K., Perlaky, L., Busch, H. Eur. J. Biochem. (1998) [Pubmed]
  10. A region of antisense RNA from human p120 cDNA with high homology to mouse p120 cDNA inhibits NIH 3T3 proliferation. Valdez, B.C., Perlaky, L., Saijo, Y., Henning, D., Zhu, C., Busch, R.K., Zhang, W.W., Busch, H. Cancer Res. (1992) [Pubmed]
  11. Genomic structure of the human proliferating cell nucleolar protein P120. Larson, R.G., Henning, D., Haidar, M.A., Jhiang, S., Lin, W.L., Zhang, W.W., Busch, H. Cancer Commun. (1990) [Pubmed]
  12. A novel role for p120 catenin in E-cadherin function. Ireton, R.C., Davis, M.A., van Hengel, J., Mariner, D.J., Barnes, K., Thoreson, M.A., Anastasiadis, P.Z., Matrisian, L., Bundy, L.M., Sealy, L., Gilbert, B., van Roy, F., Reynolds, A.B. J. Cell Biol. (2002) [Pubmed]
  13. Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis. Tucker, E., Buda, A., Janghra, B., Cpoad, J., Moorghan, M., Havler, M., Dettmar, P., Pignatelli, M. The Proceedings of the Nutrition Society. (2003) [Pubmed]
  14. Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Rimm, D.L., Koslov, E.R., Kebriaei, P., Cianci, C.D., Morrow, J.S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  15. Intranucleolar localization of human proliferating cell nucleolar antigen p120. Ochs, R.L., Reilly, M.T., Freeman, J.W., Busch, H. Cancer Res. (1988) [Pubmed]
  16. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling. Chen, X., Bonne, S., Hatzfeld, M., van Roy, F., Green, K.J. J. Biol. Chem. (2002) [Pubmed]
  17. Identification of Src phosphorylation sites in the catenin p120ctn. Mariner, D.J., Anastasiadis, P., Keilhack, H., Böhmer, F.D., Wang, J., Reynolds, A.B. J. Biol. Chem. (2001) [Pubmed]
  18. Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23. Valdez, B.C., Perlaky, L., Henning, D., Saijo, Y., Chan, P.K., Busch, H. J. Biol. Chem. (1994) [Pubmed]
  19. Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. Lampugnani, M.G., Corada, M., Andriopoulou, P., Esser, S., Risau, W., Dejana, E. J. Cell. Sci. (1997) [Pubmed]
  20. p120-Catenin regulates clathrin-dependent endocytosis of VE-cadherin. Xiao, K., Garner, J., Buckley, K.M., Vincent, P.A., Chiasson, C.M., Dejana, E., Faundez, V., Kowalczyk, A.P. Mol. Biol. Cell (2005) [Pubmed]
  21. Endogenous N-cadherin in a subpopulation of MDCK cells: distribution and catenin complex composition. Youn, Y.H., Hong, J., Burke, J.M. Exp. Cell Res. (2005) [Pubmed]
  22. Role of p120-catenin in cadherin trafficking. Xiao, K., Oas, R.G., Chiasson, C.M., Kowalczyk, A.P. Biochim. Biophys. Acta (2007) [Pubmed]
  23. ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes. Mariner, D.J., Wang, J., Reynolds, A.B. J. Cell. Sci. (2000) [Pubmed]
  24. Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family. Hatzfeld, M., Kristjansson, G.I., Plessmann, U., Weber, K. J. Cell. Sci. (1994) [Pubmed]
  25. Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. Sarrió, D., Moreno-Bueno, G., Sánchez-Estévez, C., Bañón-Rodríguez, I., Hernández-Cortés, G., Hardisson, D., Palacios, J. Hum. Pathol. (2006) [Pubmed]
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