Alternative transcription initiation and splicing variants of the DHRS4 gene cluster

2009 ◽  
Vol 29 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Qiaoxia Zhang ◽  
Yifan Li ◽  
Gefei Liu ◽  
Xiaoyuan Xu ◽  
Xuhong Song ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Gene Cluster ◽  
Transcription Initiation ◽  
Expression Patterns ◽  
Cpg Islands ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Alternative Transcription ◽  
Splicing Variants ◽  
Copy Gene

The DHRS4 (short-chain dehydrogenase/reductase superfamily member 4) gene cluster, consisting of DHRS4 and its copy gene DHRS4L2, is localized on 14q11.2. The DHRS4 gene product NADP(H)-dependent retinol oxidoreductase participates in the metabolism of retinoids. The expression patterns of the DHRS4 gene cluster were investigated in human neuroblastoma cells. Transcript analysis of the DHRS4 gene cluster using 3′- and 5′-RACE (rapid amplification of cDNA ends), reverse transcription-PCR and bioinformatics approaches showed an alternative transcription start site in the copy gene DHRS4L2 which generates two transcripts, DHRS4A1 (GenBank® nucleotide sequence database accession number AY616183) and DHRS4A2 (AY943857), together with at least six alternative splicing variants (DHRS4A_v1–6) (AY920361, AY920362, DN237886, DN237887, DN237890 and DN237892 respectively), resulted from alternative splicing. DHRS4A1 and DHRS4A2 were specifically transcribed in neuroblastoma cells. RNA structural analysis of DHRS4A1 and DHRS4A2 suggested that they are non-coding RNAs. Expression analysis of DHRS4 by quantitative real-time PCR and Western blotting showed a lack of correlation between the levels of transcription and translation in the tissues examined. Bisulfite genomic sequencing PCR experiments indicated that the expression of DHRS4L2 was regulated by methylation of its CpG islands.

scholarly journals Prostaglandin J2 Alters Pro-survival and Pro-death Gene Expression Patterns and 26 S Proteasome Assembly in Human Neuroblastoma Cells

2006 ◽  
Vol 281 (30) ◽  
pp. 21377-21386 ◽  
Author(s):  
Zhiyou Wang ◽  
Virginie M. Aris ◽  
Kenyon D. Ogburn ◽  
Patricia Soteropoulos ◽  
Maria E. Figueiredo-Pereira
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Neuroblastoma Cells ◽  
Gene Expression Patterns ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Prostaglandin J2

scholarly journals Tandemly repeated exons encode 81-base repeats in multiple, developmentally regulated Schistosoma mansoni transcripts.

1988 ◽  
Vol 8 (11) ◽  
pp. 4745-4755 ◽  
Author(s):  
R E Davis ◽  
A H Davis ◽  
S M Carroll ◽  
A Rajkovic ◽  
F M Rottman
Keyword(s):  
Alternative Splicing ◽  
Schistosoma Mansoni ◽  
Base Pair ◽  
Transcription Initiation ◽  
Tandem Repeats ◽  
Developmentally Regulated ◽  
Alternative Transcription ◽  
Exon Usage ◽  
The One ◽  
Base Insertion

The adult Schistosoma mansoni cDNA clone 10-3 encodes an antigen that is recognized by sera from infected humans. We characterized multiple developmentally regulated transcripts homologous to the 10-3 cDNA and portions of the complex genomic loci encoding those transcripts. Transcripts of approximately 950, 870, and 780 nucleotides were expressed in adults, whereas only the 780-nucleotide transcript was observed in the larval stage. These transcripts were highly similar, containing variable numbers of identical direct tandem repeats of 81 bases. Although the sequence of the repeating elements and sequences 3' to them were identical in all the transcripts, sequences 5' of the repeating elements exhibited variations, including a 27-base insertion, alternative start sites for transcription, and alternate 5' exon usage. These transcripts appeared to be derived in part by the developmentally controlled alternative splicing of small exons and the use of alternative transcription initiation sites from the one or two complex loci of at least 40 kilobase pairs. Each 81-base repeat in the transcripts was encoded by three dispersed 27-base-pair exons. These 27-base-pair exons were contained within highly conserved, reiterated 3-kilobase-pair genomic tandem arrays.

Tandemly repeated exons encode 81-base repeats in multiple, developmentally regulated Schistosoma mansoni transcripts

1988 ◽  
Vol 8 (11) ◽  
pp. 4745-4755
Author(s):  
R E Davis ◽  
A H Davis ◽  
S M Carroll ◽  
A Rajkovic ◽  
F M Rottman
Keyword(s):  
Alternative Splicing ◽  
Schistosoma Mansoni ◽  
Base Pair ◽  
Transcription Initiation ◽  
Tandem Repeats ◽  
Developmentally Regulated ◽  
Alternative Transcription ◽  
Exon Usage ◽  
The One ◽  
Base Insertion

The adult Schistosoma mansoni cDNA clone 10-3 encodes an antigen that is recognized by sera from infected humans. We characterized multiple developmentally regulated transcripts homologous to the 10-3 cDNA and portions of the complex genomic loci encoding those transcripts. Transcripts of approximately 950, 870, and 780 nucleotides were expressed in adults, whereas only the 780-nucleotide transcript was observed in the larval stage. These transcripts were highly similar, containing variable numbers of identical direct tandem repeats of 81 bases. Although the sequence of the repeating elements and sequences 3' to them were identical in all the transcripts, sequences 5' of the repeating elements exhibited variations, including a 27-base insertion, alternative start sites for transcription, and alternate 5' exon usage. These transcripts appeared to be derived in part by the developmentally controlled alternative splicing of small exons and the use of alternative transcription initiation sites from the one or two complex loci of at least 40 kilobase pairs. Each 81-base repeat in the transcripts was encoded by three dispersed 27-base-pair exons. These 27-base-pair exons were contained within highly conserved, reiterated 3-kilobase-pair genomic tandem arrays.

scholarly journals Alternative splicing variants of dual specificity tyrosine phosphorylated and regulated kinase 1B exhibit distinct patterns of expression and functional properties

2003 ◽  
Vol 372 (3) ◽  
pp. 881-888 ◽  
Author(s):  
Susanne LEDER ◽  
Hanna CZAJKOWSKA ◽  
Barbara MAENZ ◽  
Katrin de GRAAF ◽  
Andreas BARTHEL ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Protein Kinases ◽  
Kinase Activity ◽  
Catalytic Domain ◽  
Expression Patterns ◽  
Neuronal Cell ◽  
Dual Specificity ◽  
Mouse Tissues ◽  
Splicing Variants

The dual specificity tyrosine phosphorylated and regulated kinase (DYRK) family of protein kinases is a group of evolutionarily conserved protein kinases that have been characterized as regulators of growth and development in mammals, Drosophila and lower eukaryotes. In the present study, we have characterized three splicing variants of DYRK1B (DYRK1B-p65, DYRK1B-p69 and DYRK1B-p75) with different expression patterns and enzymic activities. DYRK1B-p65 and DYRK1B-p69 exhibited similar, but not identical, patterns of expression in mouse tissues, with the highest protein levels found in the spleen, lung, brain, bladder, stomach and testis. In contrast, DYRK1B-p75 was detected specifically in skeletal muscles, in the neuronal cell line GT1-7 and also in differentiated, adipocyte-like 3T3-L1 cells, but not in undifferentiated 3T3-L1 preadipocytes. A comparison of the mouse and human Dyrk1b genomic and cDNA sequences defined the alternative splicing events that produce the variants of DYRK1B. In DYRK1B-p75, transcription starts with exon 1B instead of exon 1A, generating a new translation start, which extends the open reading frame by 60 codons. This gene structure suggests that alternative promoters direct the expression of DYRK1B-p69 and DYRK1B-p75. Both splicing variants exhibited kinase activity in vitro and contained phosphotyrosine when expressed in COS-7 cells. Owing to differential recognition of the 3′-splice site in exon 9, DYRK1B-p65 differs from DYRK1B-p69 by the absence of 40 amino acids within the catalytic domain. DYRK1B-p65 lacked kinase activity in vitro and did not contain phosphotyrosine. DYRK1B-p69 and DYRK1B-p75 stimulated reporter gene activity driven by the forkhead in rhabdosarcoma (FKHR)-dependent glucose-6-phosphatase promoter more strongly when compared with DYRK1B-p65, indicating that the DYRK1B splicing variants exhibit functional differences.

Expression patterns of microRNAs are altered in hypoxic human neuroblastoma cells

2010 ◽  
Vol 26 (12) ◽  
pp. 1179-1184 ◽  
Author(s):  
Tetsuya Yamagata ◽  
Jyoji Yoshizawa ◽  
Shinsuke Ohashi ◽  
Katsuhiko Yanaga ◽  
Takao Ohki
Keyword(s):  
Expression Patterns ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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