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Changwei Liu, Assistant Professor

Ph.D. (1998), Chinese Academy of Sciences
 

 

 

Contact Info:

Molecular Biology
University of Colorado

Changwei Liu, Ph.D.  Research One South
(RC1-South), Room 9104 Changwei.Liu@ucdenver.edu Phone: 303-724-3208

The ubiquitin-proteasome pathway is responsible for degradation of more than 80% of intracellular proteins in eukaryotes. It plays important roles in protein quality control by degrading damaged proteins, and also controls a variety of cellular processes by temporal degradation of critical regulatory proteins involving in cell cycle progression, apoptosis, and development. Failure of this system may cause numerous human diseases, such as cancers, neurodegenerative diseases, and inflammatory diseases.

Usually, proteins are modified by polyubiquitin chain(s) by a cascade of enzymatic reactions including ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin protein ligase (E3). Polyubiquitinated proteins are degraded by the 26S proteasome, a 2.4 MDa complex composed of the 20S proteolytic complex and the 19S (PA700) regulatory complex. The 20S proteasome has a barrel-shaped structure arranged as heptameric abba rings. The catalytic sites are located in the central b rings. The access into the catalytic sites is occluded by a gate formed by interaction of N-termini of asubunits. The gate can be opened by interaction with PA700, an 18-subunit complex with multiple activities, including polyubiquitin chain binding activity, deubiquitination activity, substrate remodeling activity, chaperon-like activity, and ATPase activity.

One of my laboratory's interests is to understand mechanisms by which the ubiquitin-proteasome pathway degrades proteins. For example, how the 26S proteasome recognizes and selects polyubiquitinated substrates, and then how the proteasome processes a substrate for degradation. We use purified mammalian proteasomes and a variety of substrates to answer these questions by biochemical and biophysical approaches.

Another laboratory interest is to understand molecular pathways for Parkinson disease (PD) pathogenesis. We are interested in studying how and why a-synuclein is aggregated in Lewy bodies of PD brains, and what is the possible role of the ubiquitin-proteasome pathway in PD pathogenesis. We use cell biological, molecular biological and biochemical approaches to explore these questions.​​​​​​​​​

 

Liu C-W., Millen L., Roman T., Novia R., Gilbert H. F., DeMartino G. N., Thomas P. J., (2002) "Conformational Remodeling of Proteasomal Substrate by PA700, the Regulatory Complex of the 26S Proteasome." J. Biol. Chem., 277, 26815-26820.

Liu C-W., Millen L., Roman T., Novia R., Gilbert H. F., DeMartino G. N., Thomas P. J., (2002) "Conformational Remodeling of Proteasomal Substrate by PA700, the Regulatory Complex of the 26S Proteasome." J. Biol. Chem., 277, 26815-26820.

Liu C-W., Corboy M., DeMartino G. N., Thomas P. J., (2003) "Endoproteolytic Activity of the Proteasome". Science, 299, 408-411.

Lee, R. J., Liu, C-W., Harty, C., McCracken, A., Römisch, K., DeMartino, G. N.,Thomas, P. J., and Brodsky, J. L. (2004) "The 19S (PA700) Cap of the 26S Proteasome is Sufficient to Retro-Translocate and Deliver a Soluble Polypeptide for ER Associated Degradation (ERAD)". EMBO J., 23, 2206-2215.

Liu C-W., Giasson B. I., Lewis K., Lee V. M., DeMartino G. N., Thomas P. J., (2005) "A Precipitating Role for Truncated a -synucleins and the Proteasome in a -Synuclein Aggregation: Implications for Pathogenesis of asynucleinopathies". J. Biol. Chem., 280, 22670-22678.

Liu, C-W., Li, X-H., Thompson, D., Wooding, K., Chang, T-L., Tan, Z., Yu H., Thomas, P. J., and DeMartino, G. N., (2006) "ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome." Mol. Cell., in press.