Disease relevance of NUCKS1

• One of these (P1), which has significant sequence homology to the cytomegalovirus IE2 protein, binds with high affinity to the N-terminal domain of CK2beta without disrupting the formation of the CK2 holoenzyme [1].
• Potato spindle tuber viroid (PSTV), a small infectios RNA, has been completely digested with RNase T1 and RNase A, and the resulting oligonucleotides have been sequenced using 5'-terminal 32p-labelling with gamma-32p ATP and T4 polynucleotide kinase, fingerprinting and controlled nuclease P1 digestion [2].
• A major determinant of neurovirulence for the GDVII strain of Theiler's virus, a murine picornavirus, was mapped to the P1 capsid protein region [3].
• Immunogenicity of synthetic peptides of Haemophilus influenzae type b outer membrane protein P1 [4].
• In the present study, we investigated whether P1 agonist-induced Cl- secretion is preserved in cystic fibrosis airway epithelium and which signalling mechanism is involved [5].

Psychiatry related information on NUCKS1

• Using this P1 phage clone as a probe, the PK428 gene was located on 1q41-42, a possible location for a human senescence gene, a gene associated with Rippling muscle disease, as well as a region associated with genetically acquired mental retardation [6].

High impact information on NUCKS1

• The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors [7].
• Passage 1 (P1) and P10 cells have identical morphology, immunophenotype, telomere length, and differentiation capacity [8].
• It appears that in adipocytes, P1 3-kinase prevents activation of GAP [9].
• Despite a negative effect on intrinsic Abl kinase activity, both P210 SH2 mutants were still able to transform the hematopoietic factor-dependent cell lines Ba/F3 and FDC-P1 to growth factor independence [10].
• Therefore, expression of the Harvey RAS oncogene in FDC-P1 myeloid cells leads to at least two pathways of cytoplasmic signaling [11].

Chemical compound and disease context of NUCKS1

• Statistical analysis revealed that the incidence of promoter hypermethylation of any single gene, of multiple genes, or of glutathione S -transferase P1 was significantly associated with atypical and anaplastic meningiomas ( P < .0001, P = .004, and P = .004, respectively) [12].
• Stimulation of chloride secretion by P1 purinoceptor agonists in cystic fibrosis phenotype airway epithelial cell line CFPEo- [5].
• Tamoxifen prevention still remains contentious, with a significant reduction in risk of breast cancer in women given tamoxifen in the NSABP P1 study but no effect in the Italian and Royal Marsden trials [13].

Biological context of NUCKS1

• In all the species investigated, the protein contains several consensus phosphorylation sites for cyclin-dependent kinases and CK-2, and we have shown that the fish protein (like mammalian NUCKS) indeed is a substrate for CDK1 and CK-2 in vitro [14].
• Characterisation of the NUCKS gene on human chromosome 1q32.1 and the presence of a homologous gene in different species [14].
• The NUCKS gene is located on human chromosome 1q32.1 and consists of seven exons and six introns [14].
• Phosphopeptide mapping and back-phosphorylation experiments employing NUCKS from HeLa interphase and metaphase cells show that the protein is phosphorylated by Cdk1 during mitosis of the cell cycle [15].
• Retroviral expression vectors carrying the tyrosine kinase oncogenes abl, fms, src, and trk abrogate the requirements of murine myeloid FDC-P1 cells for interleukin-3 (IL-3) [16].

Anatomical context of NUCKS1

• We have isolated variant cell lines from FDC-P1 that grow in response to phorbol myristate acetate (PMA) [17].
• Preincubation of human granules with calcium, a treatment which totally inactivates the hemolytic and cytotoxic activity of murine lymphocyte granules [perforin 1 (P1)] had no effect on human LAK granule cytotoxicity for nucleated cells [18].
• In addition, Northern blot analysis of polyadenylated RNA isolated from human LAK cells using a murine P1 complementary DNA probe showed a cross-hybridizing 2.8- to 3.0-kilobase mRNA species identical in size to murine P1 mRNA [18].
• Transcriptional start sites were identified in parathyroid gland and TT cells; that for promoter P1 lies 27 bp downstream of a TATA box, whereas that for promoter P2, which lacks a TATA box, lies in a GC-rich region [19].
• All hydrophobic amino acid substitutions were transforming when tested in FDC-P1 cells yet inactivating when tested in Rat-2 fibroblasts [20].

Associations of NUCKS1 with chemical compounds

• We have previously reported transformation to growth factor-independent proliferation in the interleukin-3 (IL-3)-dependent cell line FDC-P1 by high-level expression of the valine 12 Harvey RAS oncogene, following from a nonautocrine mechanism [11].
• Like the papain protease family, SspB cleaved substrates with a hydrophobic amino acid at P2 but had a strong preference for arginine at P1 [21].
• The present work describes the detection, purification, and characterization of a serine endopeptidase with preference for a phosphoserine in the P1' position of the substrate [22].
• The site P1 (position -1 relative to the cleavage site) is mainly leucine [23].
• The effects of P1 and verapamil on drug accumulation in MCF7-MDR cells were additive [24].

Analytical, diagnostic and therapeutic context of NUCKS1

• Both data searches and Western immunoblotting experiments show that a homologous protein is present in fish, amphibians, and birds but not in insects and yeast, suggesting that NUCKS is a vertebrate specific gene [14].
• Northern blot analyses revealed that human and rat tissues contain three NUCKS transcripts varying in size from 1.5 to 6.5 kb [15].
• By partial sequence analysis, this protein was identified as the 60 kDa human heat-shock protein (hsp) that is the P1 mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa hsp [25].
• Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data [26].
• Chromatin immunoprecipitation assay results also confirm that LMP1 activates P1 promoter via the JNK-AP-1 pathway [27].

References