Dr. Ziyin Li
The University of Texas Health Science Center at Houston
Department of Microbiology and Molecular Genetics
- Cell cycle regulation in trypanosomes
My laboratory is mainly interested in understanding the molecular mechanisms of mitosis and cytokinesis. We use Trypanosoma brucei, a unicellular microbial eukaryote and the causative agent of human sleeping sickness, as a model system to address the fundamental questions of how mitosis and cytokinesis are regulated and coordinated during cell division. The advantage of using T. brucei as a model is that this organism is evolutionarily ancient, and thus it provides a unique distant reference point for dissecting crucial biological processes. The current focus is on the cell cycle regulatory pathways consisting of protein kinases such as Aurora B kinase, Polo-like kinase and Tousled-like kinase, spindle-associated motor proteins, and ubiquitin ligases.
We are also interested in the role of ubiquitin-dependent and -independent proteolysis in various cell biological processes. ATP-dependent protease complexes are present in all three kingdoms of life where they ride the cell of mis-folded or damaged proteins and control the level of certain regulatory proteins. These proteases include the 26S proteasome in eukaryotes, Archaea, and Actinomycetales and the HslVU protease in eubacteria. Currently we are investigating the function and regulation of various ubiquitin-dependent pathways and the ubiquitin-independent HslVU-mediated proteolysis pathway in T. brucei. The current focus is on three proteolytic pathways: the Cullin-RING ubiquitin ligase (CRL) and the anaphase-promoting complex/cyclosome (APC/C) on cell cycle control and HslVU protease on mitochondrial DNA replication licensing.
We use a combination of genetics, biochemistry, cell biology, molecular biology, and proteomics to elucidate the molecular and cellular basis of cell division in trypanosomes, which hopefully could provide a few excellent drug targets for chemotherapy.
Li Z. (2012) Regulation of the cell division cycle in Trypanosoma brucei. Invited review. Eukaryotic Cell, 11: 1180-1190
Hu H., Hu L., Yu Z., Chasse A.E., Chu F., and Li Z. (2012) An orphan kinesin in trypanosomes cooperates with a kinetoplastid-specific kinesin to maintain cell morphology through regulating subpellicular microtubules. Journal of Cell Science, 125: 4126-4136
Hu L., Hu H., and Li Z. (2011) A kinetoplastid-specific kinesin is required for cytokinesis and for maintenance of cell morphology in Trypanosoma brucei. Molecular Microbiology, 83: 565-578
Yu Z., Liu Y., and Li Z. (2011) Structure-function relationship of the Polo-like kinase in Trypanosoma brucei. Journal of Cell Science, 125: 1519-1530
Dang H.Q. and Li Z. (2011) The Cdc45/Mcm2-7/GINS complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex. Journal of Biological Chemistry, 286: 32424-32435
Li Z., Umeyama T., Li Z., and Wang C.C. (2010) Polo-like kinase guides cytokinesis in Trypanosoma brucei through an indirect means. Eukaryotic Cell, 9: 705-716
Li Z, Umeyama T, and Wang CC. (2009) The Aurora kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation. PLoS Pathogens, 5(9):1000575
Li Z., Umeyama T., and Wang C.C. (2008) The chromosomal passenger complex and a mitotic kinesin interact with the Tousled-like kinase in trypanosomes to regulate mitosis and cytokinesis.PLoS ONE, 3: e3814
Li Z., and Wang C.C. (2008) KMP-11, a basal body and flagellar protein, is required for cell division in Trypanosoma brucei. Eukaryotic Cell, 7: 1941-1950
Li Z, Lee JH, Chu F, Burlingame AL, Günzl A, and Wang CC. (2008) Identification of a novel chromosomal passenger complex and its unique localization during cytokinesis in Trypanosoma brucei. PLoS ONE, 3(6): e2354
Li Z, Lindsay ME, Motyka SA, Englund PT, and Wang CC. (2008) Identification of a bacterial-like HslVU protease in the mitochondria of Trypanosoma brucei and its role in mitochondrial DNA replication. PLoS Pathogens, 4(4): e1000048
Li Z, Gourguechon S, and Wang CC. (2007) Tousled-like kinase in a microbial eukaryote regulates spindle assembly and S-phase progression by interacting with Aurora kinase and chromatin assembly factors. Journal of Cell Science, 120: 3883-3894