PMID- 12890557
OWN - NLM
STAT- MEDLINE
DCOM- 20031204
LR  - 20220330
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1628
IP  - 2
DP  - 2003 Jul 28
TI  - The chromosome 21 transcription factor ETS2 transactivates the beta-APP promoter: 
      implications for Down syndrome.
PG  - 105-10
AB  - The gene that codes for beta-amyloid precursor protein (beta-APP), a protein 
      centrally involved in senile plaque formation in Down syndrome (DS) and 
      Alzheimer's disease (AD), is located on chromosome 21. In DS beta-APP expression 
      is three- to fourfold higher than what is expected from the 1.5-fold increased 
      gene load, suggesting that other genes on chromosome 21 directly or indirectly 
      can further up-regulate beta-APP. Here we show that the chromosome 21 
      transcription factor ETS2 transactivates the beta-APP gene via specific Ets 
      binding sites in the beta-APP promoter and, in this respect, cooperates with the 
      transcription factor complex AP1. We further show that brains and primary 
      neuronal cultures from Ets2 transgenic mice, as well as 3T3 fibroblasts that 
      overexpress ETS2, display molecular abnormalities also seen in DS, such as 
      elevated expression of beta-APP protein, an increase in presenilin-1 and 
      increased beta-amyloid production. We conclude that ETS2 is a transcriptional 
      regulator of beta-APP and that overexpression of ETS2 in DS may play a role in 
      the pathogenesis of the brain abnormalities in DS and possibly AD.
FAU - Wolvetang, E W
AU  - Wolvetang EW
AD  - Centre for Functional Genomics and Human Disease, Monash Institute of 
      Reproduction and Development, Monash University, Monash Medical Center, 246 
      Clayton Road, 3168, Clayton, Australia. ernst.wolvetang@med.monash.edu.au
FAU - Bradfield, O M
AU  - Bradfield OM
FAU - Tymms, M
AU  - Tymms M
FAU - Zavarsek, S
AU  - Zavarsek S
FAU - Hatzistavrou, T
AU  - Hatzistavrou T
FAU - Kola, I
AU  - Kola I
FAU - Hertzog, P J
AU  - Hertzog PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ERF protein, human)
RN  - 0 (ETS2 protein, human)
RN  - 0 (Ets2 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 0 (Proto-Oncogene Protein c-ets-2)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - 3T3 Cells
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/biosynthesis/*genetics
MH  - Animals
MH  - Binding Sites
MH  - Brain/metabolism
MH  - Chromosomes, Human, Pair 21/*genetics
MH  - *DNA-Binding Proteins
MH  - Down Syndrome/*genetics
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Presenilin-1
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Protein c-ets-2
MH  - Proto-Oncogene Proteins/biosynthesis/*physiology
MH  - *Repressor Proteins
MH  - Trans-Activators/biosynthesis/*physiology
MH  - Transcription Factor AP-1/metabolism
MH  - *Transcription Factors
MH  - Transcriptional Activation
EDAT- 2003/08/02 05:00
MHDA- 2003/12/05 05:00
CRDT- 2003/08/02 05:00
PHST- 2003/08/02 05:00 [pubmed]
PHST- 2003/12/05 05:00 [medline]
PHST- 2003/08/02 05:00 [entrez]
AID - S0167478103001210 [pii]
AID - 10.1016/s0167-4781(03)00121-0 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2003 Jul 28;1628(2):105-10. doi: 
      10.1016/s0167-4781(03)00121-0.