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Faculty
 Bing
Hao
Assistant Professor, Molecular, Microbial & Structural Biology
bhao@uchc.edu
Areas of Interest:
Our research focuses on understanding how the cell cycle is regulated by
ubiquitin-mediated proteolysis using x-ray crystallography as a primary
tool. Progression through the cell cycle is coordinated by the cyclin-dependent
kinases (CDKs) and their activating cyclin subunits as well as a series
of CKI inhibitors. Control of the oscillations of the cyclins and CKIs
by ubiquitin-dependent proteolysis plays a critical role in cell cycle
regulation. Deregulation of the cyclins and CKIs can cause aberrant
proliferation and genomic instability. Indeed, the eukaryotic cell cycle
is one of the most frequently altered cellular processes identified in
cancer.
Proteins degraded by the ubiquitin-mediated proteolysis must be
covalently linked to the small protein ubiquitin. Ubiquitin serves as a
molecular tag that marks proteins for degradation by the 26S proteasome.
The selection of substrates for ubiquitination is prescribed by a
specific class of enzymes called ubiquitin-protein ligases (also known
as E3s). Most E3 ligases comprise a large superfamily of protein-protein
complexes. They bind the substrate protein and a cognate ubiquitin-conjugating
enzyme (E2), and catalyze the transfer of ubiquitin from the E2 to
specific lysine residues within the substrate. Thus E3s are responsible
for both ubiquitin transfer and specific recognition of each of the
target proteins. However, the molecular details underlying these two
processes remain poorly understood.
The overall goal of our research is to use SCF ubiquitin ligases as a
model system to elucidate the structural and mechanistic basis of
substrate recognition, lysine specificity, ubiquitin transfer, and the
role of CDK in CKI degradation. Our long-term objective is to gain a
detailed understanding of the structure, function, and regulation of APC/C
and Cul3-based ubiquitin ligases, and to use this knowledge to elucidate
how defects of the ubiquitin system can lead to cancer and
neurodegenerative diseases.
If you are interested in conducting postdoctoral or graduate research in
our laboratory or would like more information, please contact Bing Hao
at bhao@uchc.edu.
Lab Rotation Projects:
1) Elucidation of the mechanism that regulates the substrate lysine
selection by E2 and E3 during ubiquitin transfer.
2) Structural characterization of the E2-SCF E3 interaction and its role
in the ubiquitin transfer process.
3) Structural studies of the SCF E3-substrate complexes.
Selected Publications:
Bing Hao, Stephanie Oehlmann, Mathew E. Sowa, J. Wade Harper, and
Nikola P. Pavletich (2007). Structure of a Fbw7-Skp1-CyclinE complex:
multisite-phosphorylated substrate recognition by SCF ubiquitin ligases.
Mol Cell 26, 131-143 (cover story).
Bing Hao, Ning Zhang, Brenda A. Schulman, Geng Wu, Julie J. Miller,
Michele Pagano, and Nikola P. Pavletich (2005). Structural basis of the
Cks1-dependent recognition of p27Kip1 by the SCFSkp2 ubiquitin ligase.
Mol. Cell 20, 9-19.
Bing Hao, Gang Zhao, Patrick Kang, Jitesh Soares, Tsuneo K. Ferguson,
Judith Gallucci, Joseph A. Krzycki, and Michael K. Chan (2004).
Reactivity and synthesis of L-pyrrolysine- the 22nd genetically-encoded
amino acid. Chemistry & Biology 11, 1317-24.
Bing Hao, Clara Isaza, Joseph Arndt, Michael Soltis, and Michael K.
Chan (2002). Structure-based mechanism of O2 sensing and ligand
discrimination by the FixL heme domain of Bradyrhizobium japonicum.
Biochemistry 41, 12952-8.
Bing Hao, Weimin Gong, Tsuneo K. Ferguson, Carey M. James, Joseph A.
Krzycki, and Michael K. Chan (2002). A new UAG-encoded residue in the
structure of a methanogen methyltransferase. Science 296, 1462-6 |
