The Promoter of Alzheimer's Disease Amyloid A4 Precursor Gene

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1988 Sep 1

PMID 3053167

Citations 62

Authors

J M Salbaum

A Weidemann

H G Lemaire

C L Masters

K Beyreuther

Affiliations

Soon will be listed here.

Abstract

The promoter of the gene for the human precursor of Alzheimer's disease A4 amyloid protein (PAD gene) resembles promoters of housekeeping genes. It lacks a typical TATA box and shows a high GC content of 72% in a DNA region that confers promoter activity to a reporter gene in an in vivo assay. Transcription initiates at multiple sites. Sequences homologous to the consensus binding sites of transcription factor AP-1 and the heat shock control element binding protein were found upstream of the RNA start sites. Six copies of a 9-bp-long GC-rich element are located between positions -200 and -100. A protein--DNA interaction could be mapped to this element. The 3.8 kb of the 5' region of the PAD gene include two Alu-type repetitive sequences. These findings suggest that four mechanisms may participate in the regulation of the PAD gene and could be of relevance for the progression of amyloid deposition in Alzheimer's disease.

Citing Articles

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

Volloch V, Rits-Volloch S Genes (Basel). 2025; 16(1.

PMID: 39858593 PMC: 11764795. DOI: 10.3390/genes16010046.

Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.

Volloch V, Rits-Volloch S Int J Mol Sci. 2024; 25(18).

PMID: 39337400 PMC: 11432332. DOI: 10.3390/ijms25189913.

ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.

Volloch V, Rits-Volloch S Int J Mol Sci. 2024; 25(11).

PMID: 38892224 PMC: 11172602. DOI: 10.3390/ijms25116036.

On the Inadequacy of the Current Transgenic Animal Models of Alzheimer's Disease: The Path Forward.

Volloch V, Rits-Volloch S Int J Mol Sci. 2024; 25(5).

PMID: 38474228 PMC: 10932000. DOI: 10.3390/ijms25052981.

Tolfenamic Acid Derivatives: A New Class of Transcriptional Modulators with Potential Therapeutic Applications for Alzheimer's Disease and Related Disorders.

Hill J, Shalaby K, Bihaqi S, Alansi B, Barlock B, Parang K Int J Mol Sci. 2023; 24(20).

PMID: 37894896 PMC: 10607430. DOI: 10.3390/ijms242015216.

References

BENDITT E, Eriksen N . Chemical classes of amyloid substance. Am J Pathol. 1971; 65(1):231-52. PMC: 2047520. View

Shivers B, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg P . Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 1988; 7(5):1365-70. PMC: 458385. DOI: 10.1002/j.1460-2075.1988.tb02952.x. View

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

Razin A, Riggs A . DNA methylation and gene function. Science. 1980; 210(4470):604-10. DOI: 10.1126/science.6254144. View

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

Dynan W, Tjian R . Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell. 1983; 32(3):669-80. DOI: 10.1016/0092-8674(83)90053-3. View

DOERFLER W . DNA methylation and gene activity. Annu Rev Biochem. 1983; 52:93-124. DOI: 10.1146/annurev.bi.52.070183.000521. View

Scholer H, Gruss P . Specific interaction between enhancer-containing molecules and cellular components. Cell. 1984; 36(2):403-11. DOI: 10.1016/0092-8674(84)90233-2. View

Karin M, Haslinger A, Holtgreve H, Richards R, Krauter P, Westphal H . Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984; 308(5959):513-9. DOI: 10.1038/308513a0. View

10.

Feinberg A, Vogelstein B . "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984; 137(1):266-7. DOI: 10.1016/0003-2697(84)90381-6. View

11.

Glenner G, Wong C . Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984; 122(3):1131-5. DOI: 10.1016/0006-291x(84)91209-9. View

12.

Chen E, Seeburg P . Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985; 4(2):165-70. DOI: 10.1089/dna.1985.4.165. View

13.

Masters C, Simms G, Weinman N, Multhaup G, McDonald B, Beyreuther K . Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985; 82(12):4245-9. PMC: 397973. DOI: 10.1073/pnas.82.12.4245. View

14.

Valerio D, Duyvesteyn M, Dekker B, Weeda G, Berkvens T, van der Voorn L . Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985; 4(2):437-43. PMC: 554205. DOI: 10.1002/j.1460-2075.1985.tb03648.x. View

15.

Masters C, Multhaup G, Simms G, Pottgiesser J, Martins R, Beyreuther K . Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 1985; 4(11):2757-63. PMC: 554575. DOI: 10.1002/j.1460-2075.1985.tb04000.x. View

16.

Giguere V, Isobe K, Grosveld F . Structure of the murine Thy-1 gene. EMBO J. 1985; 4(8):2017-24. PMC: 554456. DOI: 10.1002/j.1460-2075.1985.tb03886.x. View

17.

Basler K, Oesch B, Scott M, Westaway D, Walchli M, Groth D . Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 1986; 46(3):417-28. DOI: 10.1016/0092-8674(86)90662-8. View

18.

Lindquist S . The heat-shock response. Annu Rev Biochem. 1986; 55:1151-91. DOI: 10.1146/annurev.bi.55.070186.005443. View

19.

Ruppert C, Goldowitz D, Wille W . Proto-oncogene c-myc is expressed in cerebellar neurons at different developmental stages. EMBO J. 1986; 5(8):1897-901. PMC: 1167056. DOI: 10.1002/j.1460-2075.1986.tb04442.x. View

20.

Staudt L, Singh H, Sen R, Wirth T, Sharp P, Baltimore D . A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986; 323(6089):640-3. DOI: 10.1038/323640a0. View