Enzyme-mediated damage repair or mitigation is commonly found in nucleic acids, while is rare in proteins. In human MAPK-ERK signaling cascade, we found that the damages through the elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) could generate aberrantly activated MEK kinases, which might alter or disrupt cell signaling. In the collaboration with researchers from University of Illinois, we discovered that human LanCL proteins could ‘trap’ these damages in proteins (Cell 2021, 184, 1-16). Through irreversible C-glutathionylation, reactive Dha/Dhb electrophiles were removed and their potentially dysregulatory effects can be deactivated. The premature death in mice with knockout lancl genes indicates that LanCLs is critical to the survival of the organism.
Dr. Yibo Zeng
Y. Zeng completed her PhD (2009) from Department of Chemistry, the University of Hong Kong on the projects: 1) The histidine- and glutamine-rich Hpn-like protein in Helicobacter pylori; 2). The mechanism of inhibiting urease activities by bismuth compounds. Then she joined Prof. Chi-Ming Che’s group in the same department as a research associate, studying the attenuation of Wnt-β catenin pathway in human cancer cells by ruthenium compounds. In 2012, she changed her research area from biological chemistry to immunology, and worked as a postdoctoral research associate in Department of Pharmacology and Molecular Sciences, Johns Hopkins University (USA) in Prof. Thomas J. August’s group. The focus of her research included the construction of novel HIV-DNA vaccines. With the help of lysosome-associated membrane proteins (LAMP), the antigenic peptide epitopes of proteins could be delivered to helper (CD4) T-cells in order to enhance the humoral and cellular immune responses. From 2018-2020, she was a postdoctoral research associate of Cardiff University, UK Catalysis Hub and University of Oxford. Her project was focused on the repair of abnormal human kinases by eukaryotic LanCL proteins. At present, she is a postdoctoral research associate in Rosalind Franklin Institute and UK Catalysis Hub under the supervision of Prof. Ben Davis (RFI) and Prof. Graham Hutchings (Cardiff).