Abstract
We describe a facile method to activate or repress transcription of endogenous genes in a quantitative and specific manner by treatment with designed regulatory proteins (DRPs), in which artificial transcription factors (ATFs) are fused to cell-penetrating peptides (CPPs). Penetration of DRPs into cells is mediated by an N-terminal CPP fused to a nuclear localization signal; a DNA-binding domain and a transactivation domain follow. The DNA-binding domain was targeted to the vascular endothelial growth factor (VEGF)-A gene. An agonist DRP was rapidly taken up by cells and transported to the nucleus; soon after, the cells began transcribing the gene and secreting VEGF-A protein in a dose-dependent manner. Multiple copies of a short oligopeptide derived from a minimal transactivation domain of human β-catenin was stronger than VP-16. The SRDX domain from the plant transcription factor, SUPERMAN, changed the DRP to a hypoxia-induced antagonist of VEGF-A. DRPs combine many of the potential benefits of transgenes with those of recombinant proteins.
| Original language | English |
|---|---|
| Pages (from-to) | 15225-15230 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 101 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - Oct 19 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
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Regulation of the endogenous VEGF-A gene by exogenous designed regulatory proteins. / Tachikawa, Kiyoshi; Schröder, Oliver; Frey, Gerhard; Briggs, Steven P.; Sera, Takashi.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 42, 19.10.2004, p. 15225-15230.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of the endogenous VEGF-A gene by exogenous designed regulatory proteins
AU - Tachikawa, Kiyoshi
AU - Schröder, Oliver
AU - Frey, Gerhard
AU - Briggs, Steven P.
AU - Sera, Takashi
PY - 2004/10/19
Y1 - 2004/10/19
N2 - We describe a facile method to activate or repress transcription of endogenous genes in a quantitative and specific manner by treatment with designed regulatory proteins (DRPs), in which artificial transcription factors (ATFs) are fused to cell-penetrating peptides (CPPs). Penetration of DRPs into cells is mediated by an N-terminal CPP fused to a nuclear localization signal; a DNA-binding domain and a transactivation domain follow. The DNA-binding domain was targeted to the vascular endothelial growth factor (VEGF)-A gene. An agonist DRP was rapidly taken up by cells and transported to the nucleus; soon after, the cells began transcribing the gene and secreting VEGF-A protein in a dose-dependent manner. Multiple copies of a short oligopeptide derived from a minimal transactivation domain of human β-catenin was stronger than VP-16. The SRDX domain from the plant transcription factor, SUPERMAN, changed the DRP to a hypoxia-induced antagonist of VEGF-A. DRPs combine many of the potential benefits of transgenes with those of recombinant proteins.
AB - We describe a facile method to activate or repress transcription of endogenous genes in a quantitative and specific manner by treatment with designed regulatory proteins (DRPs), in which artificial transcription factors (ATFs) are fused to cell-penetrating peptides (CPPs). Penetration of DRPs into cells is mediated by an N-terminal CPP fused to a nuclear localization signal; a DNA-binding domain and a transactivation domain follow. The DNA-binding domain was targeted to the vascular endothelial growth factor (VEGF)-A gene. An agonist DRP was rapidly taken up by cells and transported to the nucleus; soon after, the cells began transcribing the gene and secreting VEGF-A protein in a dose-dependent manner. Multiple copies of a short oligopeptide derived from a minimal transactivation domain of human β-catenin was stronger than VP-16. The SRDX domain from the plant transcription factor, SUPERMAN, changed the DRP to a hypoxia-induced antagonist of VEGF-A. DRPs combine many of the potential benefits of transgenes with those of recombinant proteins.
UR - http://www.scopus.com/inward/record.url?scp=6344227879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=6344227879&partnerID=8YFLogxK
U2 - 10.1073/pnas.0406473101
DO - 10.1073/pnas.0406473101
M3 - Article
C2 - 15475575
AN - SCOPUS:6344227879
VL - 101
SP - 15225
EP - 15230
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 42
ER -