学术报告
题目：Ankyrin repeats signal “SMRT”ly to connect p53 and NFkB in infection and cancer
报告人：Xin Lu
Ludwig Institute for Cancer Research, Oxford Branch,
University of Oxford
时间：2014年7月7日（周一），14:00-15:00 PM
地点：生命科学学院411会议室
Around 20% of human cancer is caused or associates with infection and one of the most known cancer-causing pathogens is the bacteria H.Pylori. The oncoprotein of H.Pylori is CagA and it is a high risk factor of gastric cancer, the second biggest cancer killer in the world. How CagA performs its oncogenic function is a key question in cancer research. Recent studies identified ASPP2 (Ankyrin repeats, SH3 domain and Prolin rich containing Protein), a haploinsufficient tumour suppressor and an activator of p53, as a cellular target of CagA.
Importantly ASPP2 is a dynamic protein and it can also enter the nucleus to bind p53 or p73 via its Ankyrin Repeats containing C-terminus without an identifiable nuclear localisation signal (NLS). The majority of nuclear import pathways are mediated by importin-cargo interactions. Yet not all nuclear proteins interact with importins. Through a detailed understanding of the regulation of the Ankyrin Repeats containing protein ASPP2 we identified a code that defines RaDAR as a novel nuclear import pathway of ankyrin repeats (AR) containing proteins. AR is a structural motif found in over 250 human proteins with diverse functions. The RaDAR (RanGDP/AR) pathway is acquired by the most common familial melanoma-associated CDKN2A mutation, leading to nuclear accumulation of mutant p16ink4a. It is frequently used by AR-containing transcriptional regulators, especially those regulating NF-ĸB/p53. All these suggest the existence of an Ankyrin repeats signaling and its role in infection and cancer.
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