Analysis of a regulatory element in the 5′‐untranslated region of the <i>bcl‐2</i> gene

Körner, Ines; Weber-Nordt, Renate; P, Pfaff; Finke, Jürgen

doi:10.1016/s0014-5793(97)00229-9

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…[21][22][23][24][25][26] Transcriptional suppression of BCL-2 may also result from modulation of the negative response element located at the 59 untranslated region. [26][27][28] ''The agreement between our immunohistochemical and in situ mRNA hybridisation findings suggests that both BCL-2 and BAX may be under transcriptional regulation in dysplastic and neoplastic oral epithelia'' BCL-2 and BCL-X L are known to have antiproliferative effects, by delaying progression to S phase from quiescence. 29 30 In addition, the antiproliferative effect of BCL-2 has been shown to inhibit tumour progression in animal tumours.…”

Section: Discussionsupporting

confidence: 54%

Loss ofBCL-2in the progression of oral cancer is not attributable to mutations

Loro

Johannessen²,

Vintermyr³

2005

J Clin Pathol

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Background: BCL-2 and BAX are important in the regulation of apoptosis. There have been reports of loss of BCL-2 in basal cells of oral epithelial dysplasia (OED) and in oral squamous cell carcinoma (OSCC), and suppression of BAX in poorly differentiated OSCC. Aim: To investigate whether loss of BCL-2 in OED and OSCC, and of BAX in poorly differentiated OSCC could be attributed to BCL-2 and BAX mutations. Methods: Immunohistochemistry and in situ hybridisation were used to confirm BCL-2 and BAX expression. DNA was extracted from archival samples of OED (n = 22) and OSCC (n = 28). The connective tissue part from each section was collected separately and used as the normal reference. Results: No mutations were detected in BCL-2 or BAX that could explain their aberrant expression at the mRNA and protein levels in OED and OSCC. The reported A/G polymorphism at codon 7 of BCL-2 was detected in 18 of 50 samples and a novel C/T polymorphism at codon 100 was detected in three of 50 samples. Conclusions: No mutations were found that could explain loss of BCL-2 in oral dysplasia and carcinoma. An unreported C/T polymorphism in BCL-2 was detected. Downregulation of BCL-2 in OED and OSCC may be the result of transcriptional regulation.

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Section: Discussionsupporting

confidence: 54%

Loss ofBCL-2in the progression of oral cancer is not attributable to mutations

Loro

Johannessen²,

Vintermyr³

2005

J Clin Pathol

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“…This is much greater than the homology between noncoding exons of most other mammalian genes (or GATA-6 exon Ib), suggesting that this region may have an evolutionarily conserved regulatory function. Although the promoters of cellular genes are classically assumed to be 5Ј to the transcriptional initiation site, there are several examples of regulatory DNA motifs, which bind transcription factors, within the transcription unit itself (43)(44)(45)(46). Moreover, sequences within noncoding exons have in a number of cases been shown to affect the rate of transcription initiation (47)(48)(49)(50).…”

Section: The 5ј-utr Does Not Affect the Rate Or Site Of Translationalmentioning

confidence: 99%

The Human and Mouse GATA-6 Genes Utilize Two Promoters and Two Initiation Codons

Brewer¹,

Gove²,

Davies³

et al. 1999

Journal of Biological Chemistry

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GATA-6 has been implicated in the regulation of myocardial differentiation during cardiogenesis. To determine how its expression is controlled, we have characterized the human and mouse genes. We have mapped their transcriptional start sites and demonstrate that two alternative promoters and 5 noncoding exons are utilized. Both transcript isoforms are expressed in the same tissue-specific and developmental stage-specific pattern, and their ratio appears similar wherever examined. The more upstream noncoding exon showed a substantial degree of homology between the two mammalian species, suggesting a conserved regulatory function. Moreover, in transfection assays we show that elements within this exon act to promote its transcription. Positive regulatory elements that effect transcription from the more downstream exon were not apparent in this assay, revealing a regulatory distinction between the two promoters. We also demonstrate alternative initiator codon usage in both the human and mouse GATA-6 genes. Both isoforms of the protein are synthesized in vitro regardless of which 5 noncoding exon is present in the RNA, although the larger protein has greater transcriptional activation potential in transfection assays. Thus, GATA-6 function in the cell is controlled by a complex interplay of transcriptional and translational regulation.

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“…The first change to the message during cytoplasmic mRNA decay is de-adenylation by the PARN (Fig. 3) (77). Loss of the poly(A) tail facilitates 5¢ decapping such that both ends of the mRNA are accessible to exonucleolytic degradation by Xrn1 in a 5¢-3¢ direction and the exosome complex in a 3¢-5¢ direction.…”

Section: Role Of Mrna Stability In the Regulation Of Gene Expressionmentioning

confidence: 99%

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

McKay

2014

Antioxidants & Redox Signaling

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Significance: Production of proteins requires the synthesis, maturation, and export of mRNAs before their translation in the cytoplasm. Endogenous and exogenous sources of DNA damage pose a challenge to the coordinated regulation of gene expression, because the integrity of the DNA template can be compromised by DNA lesions. Cells recognize and respond to this DNA damage through a variety of DNA damage responses (DDRs). Failure to deal with DNA damage appropriately can lead to genomic instability and cancer. Recent Advances: The p53 tumor suppressor plays a dominant role in DDR-dependent changes in gene expression, but this transcription factor is not solely responsible for all changes. Recent evidence indicates that RNA metabolism is integral to DDRs as well. In particular, post-transcriptional processes are emerging as important contributors to these complex responses. Critical Issues: Transcriptional, post-transcriptional, and translational regulation of gene expression is subject to changes in response to DNA damage. How these processes are intertwined in the unfolding of DDR is not fully understood. Future Directions: Many complex regulatory responses combine to determine cell fate after DNA damage. Understanding how transcriptional, post-transcriptional, and translational processes interdigitate to create a web of regulatory interactions will be one of the key challenges to fully understand DDRs. Antioxid. Redox Signal. 20, 640-654.

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Analysis of a regulatory element in the 5′‐untranslated region of the bcl‐2 gene

Cited by 7 publications

References 15 publications

Loss ofBCL-2in the progression of oral cancer is not attributable to mutations

Loss ofBCL-2in the progression of oral cancer is not attributable to mutations

The Human and Mouse GATA-6 Genes Utilize Two Promoters and Two Initiation Codons

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

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