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Dr. Yuxin Yin

Event Start: Oct 10, 2018 1:00 pm
Location: School of Medicine, 132A


Dr. Yuxin Yin
University Professor and Dean
School of Basic Medical Sciences
Director, Institute of Systems Biomedicine
Peking University Health Science Center
Beijing, P.R. China



PTEN Family in Cancer and Beyond

Nuclear PTEN is essential for the maintenance of chromosomal stability. PTEN contains an N-terminal phosphatase domain that dephosphorylates PIP3 and a C-terminal region with less defined function. We have generated a mouse model with heterozygous deletion of the Pten C-terminal domain of PTEN.   The Pten mutant mice undergo genomic instability and develop spontaneous tumors. We also found that Pten C terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 facilitates malignancy and promotes metastasis, suggesting that PTEN and p53 play different roles in suppression of tumor development. We have recently found that PTEN controls DNA replication progression through MCM2.  PTEN also stabilizes replication forks through RPA1.  We propose that PTEN is a regulator of DNA replication and protector of replication forks.  Our data highlights a new mechanism by which PTEN maintains genomic stability and suppresses tumorigenesis.  In our recent studies, we have revealed a mechanism of alternative protein translation, through which we identified a PTEN isoform with novel functions. A CUG codon upstream of and in-frame with the coding region of canonical PTEN initiates translation of an N-terminally extended form of PTEN, which we have designated PTEN. We found that eukaryotic translation initiation factor 2A (eIF2A) controls PTENa synthesis and a CUG-centered palindromic motif is required in this process. PTENa induces cytochrome c oxidase activity and ATP production in mitochondria. Deletion of PTENa impairs mitochondrial respiratory chain function. Our data provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes.  These results suggest that mammalian cells can use alternate translation initiation mechanisms to produce isoforms of protein with distinct functions.
 
 
Wednesday October 10th, 2018
School of Medicine, Room 132A
1:00 - 2:00 pm