Disease relevance of NOL1

• To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray [1].
• Cytoplasmic p120 strongly associated with complete loss of E-CD and beta-catenin not only in lobular carcinoma and its metastases but also in atypical lobular hyperplasias [1].
• Immunostaining of E-cadherin; alpha-, beta-, and gamma-catenins; and p120 showed a membranous pattern of reactivity and generally stronger in normal pituitaries than in prolactinomas [2].
• Several viral transforming proteins, including the src protein of Rous sarcoma virus, the p120 protein of Abelson leukaemia virus and the middle T antigen of polyoma virus, are phosphorylated by associated tyrosine kinases [3].
• PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro [4].

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

• 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 [8].
• Protein p120 is a proliferation-related nucleolar protein which is detectable early in the G1 phase of the cell cycle and peaks early in the S phase [9].
• The two ends of the p120 molecule had less homology in their nucleotide and amino acid sequences [10].
• A gene for human proliferating cell nucleolar protein p120 has been isolated from a human genomic library using p120 cDNA as a probe [11].
• The rescue efficiency was enhanced by increased levels of p120, and reduced by the presence of the phosphorylation domain, a region previously postulated to confer negative regulation [12].

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

• E-cadherin mRNA levels were unaffected by p120 expression, but E-cadherin half-life was more than doubled [12].
• Inhibition of P-tyr phosphatases (PTPases) by PV markedly augmented the P-tyr content of VE-cadherin, which bound p120 and beta-catenin more efficiently, but not plakoglobin [19].
• ARVCF also completely lacked the ability to induce the cell-branching phenotype associated with overexpression of p120 [23].
• The predicted amino acid sequence of human B6P shows strong sequence homology with a murine p120 protein, which is a substrate of protein tyrosine kinase receptors and of p60v-src [24].
• Here, we evaluated the immunoreactivity of cadherins (E-, P-, and N-cadherin and cadherin-11) and catenins (alpha-, beta-, and gamma-catenin and p120) in 86 ovarian tumors [25].

Analytical, diagnostic and therapeutic context of NOL1

• In insect Sf9 cells, recombinant p120 and MSP58 proteins associated with each other, confirming the results of the yeast two-hybrid assay [9].
• However, high resolution immunoelectron microscopy demonstrated that protein p120 staining delineated a network of 20-30-nm diameter beaded fibrils distributed throughout the nucleolus [15].
• By indirect immunofluorescence, protein p120 was localized diffusely throughout all interphase nucleoli [15].
• After treatment, p120 shifted from the cytoplasm to the membrane, where it colocalized with endogenous E-CD [1].
• Surprisingly, despite apparently ubiquitous expression, ARVCF was at least tenfold less abundant than p120 in a wide variety of cell types, and was difficult to detect by immunofluorescence unless overexpressed [23].

References