Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saccharomyces cerevisiae general regulatory factor CP1 (encoded by the gene CEP1) is required for optimal chromosome segregation and methionine prototrophy. MET16-CYC1-lacZ reporter constructs were used to show that MET16 5'-flanking DNA contains a CP1-dependent upstream activation sequence (UAS). Activity of the UAS required an intact CP1-binding site, and the effects of cis-acting mutations on CP1 binding and UAS activity correlated. In most respects, MET16-CYC1-lacZ reporter gene expression mirrored that of chromosomal MET16; however, the endogenous gene was found to be activated in response to amino acid starvation (general control). The latter mechanism was both GCN4 and CP1 dependent. MET25 was also found to be activated by GCN4, albeit weakly. More importantly, MET25 transcription was strongly CP1 dependent in gcn4 backgrounds. The modulation of MET gene expression by GCN4 can explain discrepancies in the literature regarding CP1 dependence of MET gene transcription. Lastly, micrococcal nuclease digestion and indirect end labeling were used to analyze the chromatin structure of the MET16 locus in wild-type and cep1 cells. The results indicated that CP1 plays no major role in configuring chromatin structure in this region, although localized CP1-specific differences in nuclease sensitivity were detected.
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PMID:Role of the Saccharomyces cerevisiae general regulatory factor CP1 in methionine biosynthetic gene transcription. 789 81

The Saccharomyces cerevisiae general regulatory factor CP1, a helix-loop-helix protein that binds the centromere DNA element I (CDEI) of yeast centromeres, is required in yeast for optimal centromere function and for methionine prototrophy. Mutant alleles of CEP1, the gene encoding CP1, were generated by linker insertion, 5'- and 3'-deletion, and random mutagenesis and assayed for DNA binding activity and their ability to confer CP1 function when expressed in yeast. A heterologous CDEI-binding protein, TFEB, was also tested for CP1 function. The results suggested that DNA binding is required for both biological functions of CP1 but is not sufficient. A direct and quantitative correlation was observed between the chromosome loss and nutritional (i.e., Met) phenotypes of strains carrying loss of function alleles, but qualitatively the chromosome loss phenotype was more sensitive to decreased CP1 expression. The data are consistent with a model in which CP1 performs the same general chromatin-related function at centromeres and MET gene promoters and is normally present in functional excess.
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PMID:Mutational analysis of the Saccharomyces cerevisiae general regulatory factor CP1. 837 88

We describe here the first case of 8p11 myeloproliferative syndrome (EMS) with t(8;9)(p11;q33), who unusually demonstrated B-lymphoblastic/monoblastic biphenotypic transformation. A 57-year-old woman was admitted because of leukocytosis and diagnosed as EMS. Bone marrow was infiltrated with myeloperoxidase (MPO)-, CD10+, CD19+, CD20+, CD34+, HLA-DR+ small lymphoblasts and MPO+, CD2+, CD4+, CD13+, CD14+, CD33+, HLA-DR+ large monoblasts. The karyotype was 46,XX,t(8;9)(p11;q33)[20] and the CEP1/FGFR1 fusion transcript between CEP1 exon 38 and FGFR1 exon 9 was detected. This case clearly indicates that the blastic transformation in EMS with t(8;9) could arise in the stem cells, which differentiate into not only myelomonocytic but also B-lymphocytic lineages.
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PMID:A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene. 1687 8

Plasma cell leukemia (PCL) is a rare malignant plasma cell disorder. Cytogenetic studies performed on plasma cell disorders are scarce and difficult because of the low proliferation rate of plasma cells (PCs). Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of chromosomal changes in PCL. To explore the molecular cytogenetic abnormalities in Chinese patients with PCL, interphase FISH studies with three probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV) and 1q12(CEP1) were retrospectively performed in 21 PCL patients. FISH with LSI IGH/CCND1 and LSI IGH/FGFR3 probes were used to detect t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with 14q32 rearrangement. Among 21 PCL patients, molecular cytogenetic aberrations were found in 18 (81.8%) patients, four (19.0%) patients simultaneously had 13q14 deletion, illegitimate IgH translocation and 1q abnormality. 13q14 deletion was detected in 13 (61.9%) cases and illegitimate 14q32 rearrangement in 16 (76.2%) including six with t(11;14) and three with t(4;14). Chromosome 1 abnormality was found in seven (33.3%) patients, one with deletion of 1q, six with at least three copies amplifications of 1q12 (Amp1q12). 14q32 rearrangement and 13q14 deletion were found concurrently in 11 (52.4%) cases. It was showed that most PCL had chromosomal abnormalities, 14q32 rearrangement, 13q14 deletion and chromosome 1 abnormality are the frequent abnormalities, and over half of the 14q32 rearrangement were t(11;14) or t(4;14). t(4;14) and 13q14 deletion were correlated in PCL. FISH is a highly sensitive technique at detecting molecular cytogenetic aberrations in PCL and should be used in the routine evaluation of PCL.
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PMID:Molecular cytogenetic aberrations in 21 Chinese patients with plasma cell leukemia. 1828 15

Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. This study was aimed to investigate the genetic aberrations in human multiple myeloma cell lines. Interphase fluorescence in situ hybridization (FISH) with probes for the regions containing 13q14 (RB-1), 13q14.3 (D13S19), 14q32 (IGHC/IGHV) , 1q12 (CEP1), 17p13 (TP53) were was used to detect 7 HMCL and 85 cases of newly diagnosed MM. FISH with LSI IGH/CCND1 , LSI IGH/FGFR3 and LSI IGH/MAF probes were used to detect t(11;14) (q13;q32) , t(4;14) (p16;q32) and t(14;16) (q32;q23) in HMCL and MM with 14q32 rearrangement. The results showed that molecular cytogenetic aberrations were found in all 7 HMCL, six (85.7%) HMCL simultaneously had 13q14, 13q14.3 deletion. Chromosome 1q21 abnormality was found in six (33.3%) HMCL with at least 3 copies amplifications. Illegitimate 14q32 rearrangement was found in five (71.4%) HMCL, including one with t(11;14), two with t(4;14) and three with t(14;16). 17p13 deletion was detected in 5 HMCL. Chromosomal changes were observed in 85.9% of the 85 cases of newly diagnosed MM. The del(13), 1q12 amplification, del(17p), 14q32 rearrangement, t(11;14), t(4;14), t(14;16) were present in 44.7%, 52.9%, 20%, 62.4%, 27.1%, 24.7% and 3.5% of the patients respectively. There was no significant difference in the prevalence of genetic abnormalities of del(13q), 14q32 rearrangement, 1q12 amplification, t(11;14), t(4;14) except del(17p) and t(14;16). It is concluded that HMCL representative of the most aggressive phase of plasma cell neoplasms accumulated a large amount of genetic aberrations. Loss of p53 are strikingly common in HMCL suggesting that the impairment of the P53 tumor suppressor pathway is an important contributor to extramedullary tumor expansion.
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PMID:[Comparative study of genetic aberrations in human multiple myeloma cell lines and newly diagnosed MM by fluorescence in situ hybridization]. 2117 60

Chromosomal instability (CIN) is known to be associated with prognosis and treatment response in breast cancer. This study was conducted to determine whether copy number gain of centromere 17 (CEP17) reflects CIN, and to evaluate the prognostic and predictive value of CIN in breast cancer. CIN status was determined by summing copy number gains of four centromeric probes (CEP1, CEP8, CEP11, and CEP16) based on fluorescence in situ hybridization and CIN scores were calculated using next generation sequencing data. High CIN was associated with adverse clinicopatholgical parameters of breast cancer. Among them, positive HER2 status, high Ki-67 index and CEP17 copy number gain were found to be independent predictors of high CIN. High CIN was associated with poor clinical outcome of the patients in the whole group, as well as in luminal/HER2-negative and HER2-positive subtypes. CEP17 copy number was significantly higher in the high-CIN-score group than in the low-CIN-score group. A positive linear correlation between the mean CEP17 copy number and the CIN score was found. In conclusion, CEP17 copy number was confirmed as a useful predictor for CIN in breast cancer, and high CIN was revealed as an indicator of poor prognosis in breast cancer.
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PMID:Centromere 17 copy number gain reflects chromosomal instability in breast cancer. 3178 14