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Zhiwu Zhu
Research Associate, Department of Environmental
Toxicology, UC Santa Cruz
Professor of Chemistry and Chemical Biology, Zhengzhou University, P.R. China
B.S. Chemistry, Nanjing Teachers University, P.R. China
M.S. Inorganic Chemistry, Zheng Zhou University, P.R. China
Ph.D. Inorganic Chemistry, University of Wisconsin-Milwaukee
Postdoctoral Fellow, University of Michigan Medical School
Email: zhiwu.zhu@gmail.com
Lab Phone: (831)459-3996 |
Research Group: Zhu Lab
Model systems of molecular mechanisms of metal homeostasis
Biochemistry & Molecular
Biology of Metal ion Toxicity
Our
primary interest is aimed at determining the molecular mechanism
by which cells sense the changes in environmental metal ion concentrations.
We are specifically interested in the signaling mechanism of copper
homeostasis, particularly how copper deprivation is sensed and
transduced, leading to the activation of the copper transporter
gene (CTR1) expression. We discovered that the copper sensing transcription
factor Mac1p is modified by phosphorylation. We are using genetic
and biochemical tools to determine the link between Mac1p phosphorylation
and its regulatory role in CTR1 transcription.
Our second interest is the coordination between copper and iron homeostasis.
We discovered that the ferrous oxidase Fet3p, a component of the yeast high-affinity
iron transporter complex, plays a critical role in copper detoxification by
catalyzing oxidation of the toxic Cu+ to less toxic Cu2+. Copper and iron homeostasis
converges at an interface consisting of counteracting Fet3p oxidase and Fre1p
reductase. We are studying how a cell coordinates the regulation of these two
genes. We are also studying iron regulation of copper transporter gene expression
to gain a comprehensive understanding of Cu-Fe interactions.
The other main research interest is to understand metabolic reorganizations
under metal ion deprivation. Our aim is to elucidate how a cell adjusts its
metabolic pathways to adapt to metal ion deficient conditions at a molecular
level, which will allow us to develop nutritional based alternative therapeutic
strategies for treating diseases. We are currently studying the impact of
iron deficiency on sugar and other cellular metabolisms.
Selected
Publications:
Shi, X., Chabarek, K., Budai, A. and Zhu, Z. (2003) Iron
Requirement for GAL Gene Induction in the Yeast Saccharomyces
cerevisiae. J. Biol. Chem.
278, 43110-43113.
Shi, X., Stoj, C., Romeo, A., Kosman, D. J. and Zhu, Z. (2003) Fre1p Cu2+
Reduction and Fet3p Cu1+ Oxidation Modulate Copper Toxicity in Saccharomyces
cerevisiae. J.
Biol. Chem 278. In press.
Zhu, Z. (2003) The distinct functions of three metal ion-binding motifs
of Mac1p in the regulation of CTR1 transcription. J. Biol. Chem.
Submitted.
Kwik-Uribe, C. L., Reaney, S., Zhu, Z. and Smith, D. (2002) Alternations
in cellular IRP-dependent iron regulation by in vitro manganese exposure
in undifferentiated
PC12 cells. Brain Research 973, 1-15.
Yonkovich, J, McKenndry, R., Shi. X. and Zhu, Z. (2002) Copper ion-sensing
transcription factor Mac1p post-translationally controls the degradation
of its target gene product Ctr1p. J. Biol. Chem. 277, 23981-23984.
Zhu, Z., Heredia, J. and Teves, R. (2002) Sensory protein modification: A new
feature in copper balancing, in Handbook of copper pharmacology and toxicology,
ed. E. J. Massaro, Human Press, Totowa, NJ, pp.475-480.
Heredia, J., Crooks, M, and Zhu, Z. (2001) Phosphorylation and Cu+-coordination
dependent DNA-binding of the transcription factor Mac1 in the regulation
of copper transport. J. Biol. Chem. 276, 8793-8797.
Zhu, Z., McKendry, R. and Chavez, C. L. (2000) Signaling in Copper Ion Homeostasis.
In Cell and Molecular Responses to Stress, vol. 1, Kenneth B. Storey and Janet
M. Storey ed. JAI Press, Stamford, CT.
Zhu, Z., Simon, L., Pena, M. O. and Thiele, D. J. (1998) Copper differentially
regulates the activity and degradation of yeast Mac1 transcription factor. J.
Biol. Chem. 273,1277-1280
.
Simon, L., Zhu, Z. and Thiele, D. J. (1997) Copper-specific transcriptional
repression of yeast genes encoding critical components in the copper transport
pathway. J. Biol. Chem. 272,15951-15958.
Zhu, Z. and Thiele, D. J. (1996) A specialized nucleosome modulates
transcription factor access to a C. glabrata metal responsive promoter. Cell
87, 459-470.
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