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 Albena Dinkova-Kostova
answer a
few questions about this month's fast breaking paper in
the field of Pharmacology & Toxicology.
The author has also
sent along images of their work.
From
•>>February 2007
Field:
Pharmacology & Toxicology
Article Title: The role of Keap1 in cellular protective responses
Authors: Dinkova-Kostova,
AT;Holtzclaw, WD;Kensler, TW
Journal: CHEM RES TOXICOL
Volume: 18
Issue: 12
Page: 1779-1791
Year: DEC 2005
* Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Lewis B & Dorothy Cullman Canc Chemoprotect
Ctr, Dept Pharmacol & Mol Sci,Sch Med, Baltimore, MD 21205 USA.
* Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Lewis B & Dorothy Cullman Canc Chemoprotect
Ctr, Dept Pharmacol & Mol Sci,Sch Med, Baltimore, MD 21205 USA.
* Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth
Sci, Baltimore, MD 21205 USA.
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 Why
do you think your paper is highly cited
?
To our knowledge, this is the first comprehensive review on
the discovery and role of a protein that functions to sense
various chemoprotective agents, thus sending a signal that
ultimately results in an increase of the levels of a battery of
cytoprotective proteins and enhanced cellular protection against
electrophiles and oxidants.
Could
you summarize the significance of your paper in layman’s terms?
The paper summarizes the development of a strategy for
protection against chronic diseases, the focus being on the
protein sensor for protective agents. It is clear that Keap1
plays a central role in regulating adaptive responses to
electrophilic and oxidative stresses.
How
did you become involved in this research, and were any problem
encountered along the way?
My involvement came during the search for the protein sensor
for inducers of cytoprotective responses.
Are
there any social or political implications for your research?
The complete understanding of the structure and function of
this protein could allow for the development of rational
strategies for protection against chronic diseases.
Albena T. Dinkova-Kostova, Ph.D.
Department of Medicine
Division of Clinical Pharmacology
Johns Hopkins University School of Medicine
Baltimore, MD, USA
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A Closer Look...
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Below
are images sent in by Albena Dinkova-Kostova which correspond with the featured
paper, or current research. |
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Figure 1:
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Figure
1:
Mechanism of phase 2 enzyme induction. In the absence of inducing stimuli the sensor protein Keap1 (green) binds and targets transcription factor Nrf2 for ubiquitination and proteasomal degradation via association with the Cullin 3 (Cul3)-based E3 ubiquitin ligase complex. Inducers react and chemically modify specific highly reactive cysteine residues of Keap1. Consequently, Keap1 loses its ability to repress transcription factor Nrf2 allowing its translocation to the nucleus, binding to the ARE (in heterodimeric combinations with members of the small Maf family of transcription factors), and ultimately the transcriptional activation of phase cytoprotective 2 genes. |
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ESI Special Topics,
February 2007
Citing URL - http://www.esi-topics.com/fbp/2007/february07-AlbenaDinkova-Kostova.html
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