Seminar: Ubiquitin-proteolytic Control of DNA Repair and Tumorigenesis
posted by Department of Chemistry for HKU and Public
Event Type: Public Lecture/Forum/Seminar/Workshop/Conference/Symposium
Event Nature: Science & Technology
Speaker: Prof. Pengbo Zhou
Professor of Pathology and Laboratory Medicine,
Pathology and Laboratory Medicine,
Weill Cornell Medical College, USA
The cullin-RING 4 (CRL4) ubiquitin ligases are vital regulators of a wide array of cellular processes, including cell cycle, cell signaling, DNA repair, and development. The CUL4A gene is often found amplified or overexpressed in breast cancer, lung cancer and many other tumor types. Our research has identified an inhibitory function of CUL4A in restricting the cellular DNA damage response capacity by orchestrating the concerted actions of nucleotide excision repair (NER) and the G1/S checkpoint, and this is achieved through selective degradation of the DDB2 and XPC DNA damage sensors and the p21/CIP1/WAF1 checkpoint effector. We generated Cul4a conditional knockout mice and observed that skin-specific Cul4a ablation dramatically increased resistance to UV-induced skin carcinogenesis. We have carried out high throughput screens for small molecules that can inhibit the CRL4A ubiquitin ligase activity and recapitulate the NER enhancement in Cul4a knockout cells and animals. Data will be presented on characterization of one class of CRL4 inhibitors and the potential use in antagonizing carcinogenesis associated with CRL4 dysregulation.
All are Welcome
|Venue||Lecture Theatre P1, CYM Chemistry Building|
Registration is not required.
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