Mark Hannink
Professor of Biochemistry
Associate Director, Fellowships and Education, Life Sciences Center
E-mail:hanninkm@missouri.edu
Office: 440E Bond Life Sciences Center
Mail: Christopher S. Bond Life Sciences Center
440E Bond Life Sciences Center
University of Missouri
Columbia, MO 65211
Phone: 573-882-7971
Fax: 573-884-3087
Lab: 573-882-1378
Educational background
| Degree | School | Location | Major |
| BS | Calvin College | Grand Rapids, Mich. | Chemistry |
| MS | University of Washington | Seattle, Wash. | Organic Chemistry |
| PhD | University of California-San Diego | La Jolla, Calif. | Biochemistry |
Notable honors and service
- Associate Director for Fellowships and Education, Life Sciences Center
- PI NIGMS-funded T32 training grant in Molecular Cell Biology
- PI NIGMS-funded Initiative for Maximizing Student Diversity (IMSD)
Research summary
My laboratory is interested in the molecular and cellular mechanisms of intracellular signal transduction. We are particularly interested in the signaling mechanism(s) that enable human cells to sense and respond to oxidative stress.
Research description
Our laboratory has identified an E3 ubiquitin ligase complex that is regulated by oxidative stress. The major substrate of this ubiquitin ligase complex is the Nrf2 transcription factor, which is brought into the ubiquitin ligase complex by the Keap1 protein. Keap1 contains redox-sensitive cysteine residues that, when modified by reactive electrophilic compounds, including reactive oxygen species (ROS), alter the ability of Keap1 to target Nrf2 for ubiquitin-dependent degradation. This leads to increased stabilization of Nrf2 and to activation of a transcriptional program that enables cells to neutralize reactive molecules and maintain cellular redox homeostasis. We have identified several new partners for Keap1, including a protein termed PGAM5 that anchors the Keap1-Nrf2 complex to the outer mitochondrial membrane. PGAM5 also regulates the morphological appearance of mitochondria. We propose that PGAM5 is a critical link between generation of ROS by mitochondria and Nrf2-dependent anti-oxidant genes. We are currently characterizing a gene knockout mouse model for PGAM5.
Selected publications
Zhang DD, Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent degradation of Nrf2 and for stabilization of Nrf2 by chemopreventive agents. Mol Cell Biol, 2003, 23: 8137-8151. [full paper]
Zhang DD, Lo SC, Cross JV, Templeton DJ, and Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 2004, 24: 10941-10953. [full paper]
Li X, Zhang DD, Hannink M, and Beamer LJ. Crystal structure of the Kelch domain of Keap1: A structural model for the substrate binding domain of BTB-Kelch substrate adaptor proteins. J Biol Chem, 2004, 279: 54750-54758. [full paper]
Zhang DD, Lo SC, Habib GM, Lieberman MW, and Hannink M. Ubiquitination of Keap1, a BTB-Kelch substrate adaptor for Cul3, targets Keap1 for degradation by a proteosome-independent pathway. J. Biol Chem, 2005, 280: 30091-9. [full paper]
Lo SC and Hannink M. Substrate adaptor recycling is required for efficient Keap1-dependent ubiquitination of Nrf2. Mol Cell Biol 2006, 26: 1235-1244. [full paper]
Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J, 2006, 25: 3605-17. [full paper]
Lo SC, Hannink M. PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J Biol Chem. 2006, 281:37893-37903. [full paper]
Lo SC and Hannink M. PGAM5 tethers a ternary complex containing Keap1 and 1 Nrf2 to mitochondria. Exp Cell Res 2008; 314:1789-1803. [full paper]
Westfall S.D., Sachdev S., Das P., Hearne L.B., Hannink M., Roberts R.M., Ezashi T. (2008) Identification of oxygen-sensitive transcriptional programs in human embryonic stem cells. Stem Cells Dev. Vol. 17 (5): 869-81
Employment opportunities
Postdoctoral opportunities
Research areas: BTB-Kelch substrate adaptor family in development, oncogenesis and neurodegeneration.
How to apply:
Electronic submission is encouraged, e-mail to hanninkm@missouri.edu
Applicants should send CV and names of two references to:
Dr. Mark Hannink
Christopher S. Bond Life Sciences Center
440E Bond Life Sciences Center
University of Missouri
Columbia, MO 65211