Tso-Pang Yao, Pharmacology and Cancer Biology

The major interest in our laboratory is to uncover novel functions for reversible protein acetylation in signal transduction. To study acetylation biology, our laboratory utilizes an integrated approach that includes cell biology, molecular, biochemical and genetic approach using tissue culture cells, mouse and drosophila as models. We have focused our effort on two major fronts. First, we study the tumor suppressor p53 to examine the regulation and function of reversible acetylation in human cancer formation. We have found that p53 acetylation is tightly regulated by various components critical in oncogenesis. We also uncovered a novel functional intersection between acetylation and ubiquitination, which together, control p53 stability and activity. The current focus of this part of study is to determine how acetylation and ubiquitination machinery "talk" to each other to achieve tumor suppression and how oncogenic mutations might impact on this cross-talk.

The second focus of the lab is to isolate and characterize the functions of novel deacetylases (HDAC). For example, we identified HDAC 6 and its family member HDAC10 as deacetylases that link cytoskeleton to the protein degradation machinery. This functional connection is important for growth factor signaling and the clearance of cytotoxic misfolded protein aggregates, which are likely the causes of neuron cell death leading to neurodegenerative disease. We also discovered that the deacetylase HDAC4 shuttles between nucleus and cytoplasm in response to specific signaling events. We found that subcellular localization of HDAC4 is likely a key factor in regulating neuron viability under different physiological conditions and developmental stages. These complex cellular and biochemical behavior of HDAC members indicate a rich biology controlled by acetylation. It is our ultimate goal to uncover how reversible acetylation regulates various important biological processes.