The role of T-cell protein tyrosine phosphatase (TC-PTP) in the nucleus /

The 45kDa isoform of TC-PTP is a ubiquitous, predominantly nuclear protein. Reports demonstrate that it can exist outside the nucleus; however, immunofluorescence and cellular fractionation techniques point to an almost exclusive residence in the nucleus, and even within the nucleolus. Though the conditions of nucleolar enrichment appear to be serum-dependent, and may involve S52 phosphorylation, the exact circumstances necessary for this localization remain unknown, though TC-PTP C216S mutant, and not an S52A/C216S double mutant had the ability to trap a phosphorylated substrate of ∼105kDa, thus encouraging further research into the identity of this phosphoprotein. There is also data implicating TC-PTP in the p53-dependent DNA damage response. TC-PTP WT pMEF's are more susceptible to apoptosis than KO pMEF's, thus suggesting a possible role as a tumor suppressor. Finally, in order to explore the physiological significance of possible non-hematopoietic roles of TC-PTP, a Cre-Lox targeting vector was constructed for the eventual generation of a conditional knockout