Research:
The Xing lab is interested in elucidating the molecular, structural and biochemical basis of diverse cell signaling pathways and regulations related to cancer and toxicity, such as phosphatase regulation, cancer cell signaling mediated by MTDH-SND1, and aryl hydrocarbon receptor (AHR) signaling. We utilize diverse multi-disciplinary biophysical, biochemical, and cell biology approaches, including x-ray crystallography, computational structural biology, enzymology, the state-of-the-art proteomics and time-lapse fluorescent imaging, aiming to gain deep mechanistic understanding and facilitate identification of novel therapeutic targets and strategies.Protein Phosphatase 2A
Protein phosphatase 2A (PP2A) is one of the most important and abundant Ser/Thr phosphatases in all eukaryotic cells with complex regulation and compositions. It plays a critical role in many essential aspects of cellular function, and deregulation of its function has been linked to many types of cancer, neurodegenerative disorders, and heart failure. PP2A participates in diverse cellular processes via formation of numerous heterotrimeric holoenzymes. Each contains a common core enzyme formed by PP2A scaffold (A) and catalytic (C or PP2Ac) subunits and a variable regulatory subunit from one of four major families (B/PR55, B′/PR61,B′′/PR72 and B′′′/Striatin). In addition to regulatory subunits, the function of PP2A is also controlled by diverse regulatory proteins, including α4, phosphatase activator (PTPA), methyltransferase (LCMT-1), esterase (PME-1), and protein chaperones. The Xing lab has pioneered in the structural biology of PP2A regulation. In addition to elucidation of the structures of PP2A holoenzymes, several important breakthroughs in the lab on the structural basis of PP2A regulation reveal a linear pathway for strict control of the biogenesis of PP2A holoenzymes.
Current PP2A projects in the lab include: 1) mechanisms regulating PP2A holoenzyme biogenesis and function; 2) protein chaperones and catalytic metal ions in the biogenesis and recycling of PP2Ac in response to cellular signaling; 3) molecular basis of substrate recognition by PP2A holoenzymes using structural, biochemical, and proteomic approaches; 4) PP2A regulation in cell signaling and signaling crosstalks to diverse pathways related to cancer and heart failure, including mTOR, MAPK, PML signaling, DNA damage response, and cell metabolism; 5) development of therapeutic strategies targeting PP2A regulation.