Home Faculty and Research Faculty by Name Qing Zhong

Qing Zhong

Assistant Professor of Biochemistry and Molecular Biology

Lab Homepage: http://mcb.berkeley.edu/labs/zhong/

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Research Interests

Programmed cell death is a normal component of the development and health of eukaryote. In programmed cell death, cells die in a controlled and regulated fashion in response to a variety of stimuli. We are focusing on two types of programmed cell death - DNA damage induced apoptosis and stress induced autophagy, especially the regulatory steps through ubiquitin and ubiquitin-like modifications. We study apoptosis and autophagy mainly through in vitro biochemical approach to map novel cellular pathways initiating these responses, then in vivo approach to further define their cellular functions and regulations. Crosstalk between these pathways is also our research interest.

Current Projects

Apoptosis: Apoptosis is type I programmed cell death initiated by cell itself following by removal of dying cells by phagocytosis. Deregulation of apoptosis is a major underlying mechanism in tumorigenesis. In response to intrinsic apoptotic signals (such as DNA damage), mitochondria is the place where apoptosis initiates. However, how are the signals from DNA damage transduced to mitochondria remains elusive.

In an effort to dissect upstream apoptotic signaling pathway to mitochondria, we identified Mcl-1 as an apical inhibitor to prevent cytochrome c release from mitochondria, a key event to initiate caspase activation. Elimination of Mcl-1 is achieved by ubiquitin-mediated proteasomal degradation. Applying Mcl-1 ubiquitination as a reporter assay, we fractionated HeLa cell extract and purified a novel HECT-containing ubiquitin ligase. We named it as Mule (Mcl-1 Ubiquitin Ligase E3). Mule is the first ubiquitin ligase isolated through functional biochemical fractionation in history. Interestingly, we found that Mule also targets p53 for degradation. Currently, we are in the process to understand the detail mechanism of Mule regulation, especially in response to DNA damage,  and its relevance to tumorigenesis. 

Autophagy: Autophagic cell death is type II programmed cell death in which cell digest themselves to death as a suicide strategy. In autophagy, the cell recycles the cytoplasm and disposes of excess or defective organelles. Autophagy is a highly regulated process critical for response to nutrient starvation, removal of protein aggregates, cellular defense against bacterial and virus invasion and therefore implicated in multiple human diseases such as cancer, diabetes, neurodegenerative diseases and infectious diseases. Two core ubiquitination-like (LC3 and ATG12) modifications play critical role in formation of autophagosome-a double membrane structure to engulf organelles, protein aggregates, and bacterial or viral particles. The regulation of these ubiquitin-like reactions is completely unknown.

We aim to reconstitute these ubiquitin-like reactions with cell extracts of human culture cells and isolate the unknown regulatory activity through biochemical fractionation and purification. We are also systemically investigating in vivo function of proteins involved in autophagy by RNA interference.

Selected Publications

JR, Kow E, Nevis KR, Lu CK, Luce KS, Zhong Q, Cook JG. (2007) Cdc6 Stability Is Regulated by the Huwe1 Ubiquitin Ligase after DNA Damage. Mol Biol Cell. 13; 3340-50.

Q, He X, Hsu JM, Xia W, Chen CT, Li LY, Lee DF, Liu JC, Zhong Q, Wang X, Hung MC. (2007) Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol. 27(11):4006-17.

Zhong Q, Gao W, Du F, Wang X. (2005) Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell, 121: 1085-1095.

Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, Wang X. (2003) Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes and Dev., 17:1475-1486.

Zhong Q, Chen C-F, Chen P-L, and Lee W-H. (2002) BRCA1 facilitates microhomology-mediated end joining of DNA double strand breaks. J Biol Chem., 277: 28641-28647.

Zhong Q, Boyer TG, Chen P-L, and Lee W-H. (2002) Deficient nonhomologous end-joining activity in cell-free extracts from Brca1-null fibroblasts. Cancer Res., 62: 3966-3970.

Chen C-F, Chen P-L, Zhong Q, Sharp ZD, and Lee W-H. (1999) Expression of BRC Repeats in Breast Cancer Cells Disrupts the BRCA2-Rad51 Complex and Leads to Radiation Hypersensitivity and Loss of G2/M Checkpoint Control. J. Biol. Chem., 274: 32931-32935.

Zhong Q, Chen C-F, Li S, Chen Y, Wang C-C, Xiao J, Chen P-L, Sharp ZD, and Lee WH. (1999) Association of BRCA1 with the hRad50-hMre11-p95 Complex and the DNA Damage Response. Science, 285: 747-750.

Last Updated 2007-09-06