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ZHU LAB
Zhiwu Zhu
487 Physical Sciences Building
Email: zhiwu.zhu@gmail.com
Lab Phone: (831) 459-3996
Lab Members
Selected Publications
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.
LAB MEMBERS
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Xiaoli
Shi
Postdoctoral Scholar
Ph.D. Environmental Toxicology, University of California, Santa Cruz
Research Interest: Metal toxicity |
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Kate Chabarek
Graduate Student Researcher
B.A. Plant Science, Cornell University
I study the kinase that phosphorylates the copper signaling protein Mac1p, as well as the iron metabolism of the protozoan Trypanosoma
brucei. |
ALUMNI
Undergraduate Student Researcher Alumni
Seiko Benner,
MCD Biology, UC Santa Cruz
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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