Study On The Molecular Mechanism Of PTPRO-a Candidate Tumor Suppressor

Protein tyrosine phosphorylation is a fundamental mechanism for numerous important aspects of eukaryote physiology. The levels of protein tyrosine phosphorylation are regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). PTPs play a crucial role in regulating cellular growth, proliferation, differentiation, migration, metabolism, cell-cell communication, immune reponse and survival. The deregulation of PTPs function is associated with tumorigenesis in different types of human cancer.PTPRO is a member of the receptor-like PTPs, and was purified and cloned in the experiment screening the specifically expressed protein in the glomerular podocyte. PTPRO is highly conserved in the vertebrates from mouse to human. In the human genome, the gene ptpro is located at 12p13.3-p13.2. There are six different mRNA variants for PTPRO, and among them there are two major forms, which are encoded by the full length PTPRO (PTPRO-FL) cDNA and the truncated PTPRO(PTPROt) cDNA respectively. The PTPRO-FL is highly expressed in the kidney and the brain, while the PTPROt is mainly in the B lymphocyte and the macrophage.It is believed that PTPRO is a candidate tumor suppressor, but the mechanism by which PTPRO functions is not fully understood. In this study, we found that the expression of the PTPRO is up-regulated in the G1/S phase in cell cycle. This implyed that PTPRO maybe play a crucial role in the transition from G1 to S phase. In the following experiments we revealed that PTPRO can repress the expression of cell cycle-associated gene, especially the E2F1 target gene cyclinE and cyclinA. We also found that PTPRO can promote the expression of p73 and p21. Altogether we draw a conclusion that PTPRO functions as a candidate tumor suppressor by its repression of cyclinE and cyclinA and its activation of p73 and p21.