Isolation and functional characterisation of the promoter region of the human prion protein gene

Mahal, Sukhvir P.; Asante, Emmanuel A.; Antoniou, Michael; Collinge, John

doi:10.1016/s0378-1119(01)00424-3

Cited by 42 publications

(53 citation statements)

References 27 publications

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“…However, little is known about the molecular pathways underlying these regulatory events. The functional characterization of the human prion promoter (Funke-Kaiser et al, 2001) identified two regulatory regions where sequence analysis revealed consensus sequences for AP-1, Sp1, and Sp2 factors (Mahal et al, 2001;Bellingham et al, 2009). Our in silico analysis of the human PRioN protein (PRNP) gene promoter also revealed a motif partly matching the binding sequence targeted by the oncogene p53.…”

Section: Introductionmentioning

confidence: 78%

p53-Dependent Transcriptional Control of Cellular Prion by Presenilins

Vincent¹,

Sunyach²,

Orzechowski³

et al. 2009

J. Neurosci.

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The presenilin-dependent ␥-secretase processing of the ␤-amyloid precursor protein (␤APP) conditions the length of the amyloid ␤ peptides (A␤) that accumulate in the senile plaques of Alzheimer's disease-affected brains. This, together with an additional presenilinmediated -secretase cleavage, generates intracellular ␤APP-derived fragments named amyloid intracellular domains (AICDs) that regulate the transcription of several genes. We establish that presenilins control the transcription of cellular prion protein (PrP c ) by a ␥-secretase inhibitor-sensitive and AICD-mediated process. We demonstrate that AICD-dependent control of PrP c involves the tumor suppressor p53. Thus, p53-deficiency abolishes the AICD-mediated control of PrP c transcription. Furthermore, we show that p53 directly binds to the PrP c promoter and increases its transactivation. Overall, our study unravels a transcriptional regulation of PrP c by the oncogene p53 that is directly driven by presenilin-dependent formation of AICD. Furthermore, it adds support to previous reports linking secretase activities involved in ␤APP metabolism to the physiology of PrP c .

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Section: Introductionmentioning

confidence: 78%

p53-Dependent Transcriptional Control of Cellular Prion by Presenilins

Vincent¹,

Sunyach²,

Orzechowski³

et al. 2009

J. Neurosci.

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“…1). The available evidence suggests that polymorphisms in these regions affect transcription of the PRNP gene [15,18,21]. In a previous study, the 23-bp insertion was found to occur more frequently in healthy cattle than BSE-affected cattle [28].…”

Section: Discussionmentioning

confidence: 94%

“…Among Holstein cattle in Japan, the 23-bp insertion has been found to have a lower allele frequency than the 23-bp deletion. We speculated that polymorphism of the 12-bp indel might affect expression levels of the PRNP gene, because the indel is in the promoter region of intron 1 and contains a putative Sp1-binding consensus sequence [9,15,18,19]. It has been reported that a GC-rich region and Sp1-binding sequence upstream of exon 1 are both important factors in PRNP transcription [1,15,18], but the effects of this Sp1 sequence in intron 1 are unclear.…”

Section: Discussionmentioning

confidence: 99%

Sequence Variation of Bovine Prion Protein Gene in Japanese Cattle (Holstein and Japanese Black)

Nakamitsu

Miyazawa

Horiuchi

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. To assess relationships between nucleotide polymorphisms of the prion protein (PRNP) gene and susceptibility to bovine spongiform encephalopathy (BSE), we investigated polymorphisms in the open reading frame (ORF) and 2 upper regions of the PRNP gene from 2 Japanese cattle breeds: 863 healthy Holstein cattle, 6 BSE-affected Holstein cattle, and 186 healthy Japanese Black (JB) cattle. In the ORF, we found single-nucleotide polymorphisms (SNPs) at nucleotide positions 234 and 576 and found 5 or 6 copies of the octapeptide repeat, but we did not find any amino acid substitutions. In the upper region, we examined 2 sites of insertion/deletion (indel) polymorphisms: a 23-bp indel in the upper region of exon 1, and a 12-bp indel in the putative promoter region of intron 1. A previous report suggests that the 23-bp indel polymorphism is associated with susceptibility to BSE, but we did not find a difference in allele frequency between healthy and BSE-affected Holstein cattle. There were differences in allele frequency between healthy Holstein and JB cattle at the 23-and 12-bp indels and at the SNPs at nucleotide positions 234 and 576, but there was no difference in allele frequency of the octapeptide repeat. We identified a unique PRNP gene lacking a 288-bp segment (96 amino acids) in DNA samples stocked in our laboratory, but this deletion was not found in any of the 1049 cattle examined in the present study. The present results provide data about variations and distribution of the bovine PRNP gene.

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“…This allows for a no-lysis protocol for assaying luciferase activity in transfected cells by simply reading the luciferase activity (when a substrate is added) of the medium. To clone the PRNP promoter fragment into pML2, primers were designed to amplify the region from Ϫ391bp to Ϫ274bp, around the ERSE-26, which was obtained from the pGL3 PRNP promoter construct, kindly given to us by the laboratory of Dr. Collinge (26). The following primers were used (restriction sites in bold): forward, 5Ј-GAG CTC TCT CCA TTA TGT AAC GGG GA-3Ј; and reverse, 3Ј-GCG AAT TCT CAG TTG ATA CCG CCT GCG G-5Ј.…”

Section: Methodsmentioning

confidence: 99%

“…The PRNP promoter contains GCrich repeats, which are common to housekeeping genes. It does not contain the core promoter TATA box sequence but does contain Sp1, Ap-1, Ap-2, and CCAAT box transcriptional binding sites (26,27). Regulatory elements include MyoD, heat shock elements (28), and metal regulatory element MTF-1 (29).…”

mentioning

confidence: 99%

Identification of a Novel Endoplasmic Reticulum Stress Response Element Regulated by XBP1

Misiewicz

Déry

Foveau

et al. 2013

Journal of Biological Chemistry

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Background: Endoplasmic reticulum (ER) stress maintains cellular protein homeostasis. Results: A novel ER stress-responsive element, ERSE-26, identified in 38 genes, is regulated by sXBP1 during ER stress. Conclusion: ER stress increases levels of prion and other proteins not previously known to be involved in the ER stress response. Significance: ERSE-26 implicates novel genes regulated by the ER stress response.

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Isolation and functional characterisation of the promoter region of the human prion protein gene

Cited by 42 publications

References 27 publications

p53-Dependent Transcriptional Control of Cellular Prion by Presenilins

p53-Dependent Transcriptional Control of Cellular Prion by Presenilins

Sequence Variation of Bovine Prion Protein Gene in Japanese Cattle (Holstein and Japanese Black)

Identification of a Novel Endoplasmic Reticulum Stress Response Element Regulated by XBP1

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