Identification and Validation of PTEN Complex, Associated Proteins

摘要

The PTEN/MMAC1/TEP1 is a tumor suppressor gene, targeted for biallelic somatic inactivation in a variety of cancers including advanced prostate adenocarcinomas among many others malignancies. PTEN is a phosphatase and has an important role in regulation of the PI3K/AKT signaling pathway, which plays a key role in regulating cellular functions including proliferation, apoptosis, glucose homeostasis, cell size, nutrient response and DNA damage. Furthermore, PTEN functions in the cell to restrict both growth and survival in absence of growth signals. Studies performed in our laboratory indicated that in addition to its 47Kda form, PTEN could be detected as a part of a >600Kda complex. Further, we have also shown that PTEN acts as an antagonist of the PI3K/AKT signaling, only when it is unphosphorylated and recruited into the large protein complex. We have identified a novel partner of the PAC. Our biochemical purification and immuno-precipitation experiments show that the p85 regulatory subunit of PI3K is a part of the PAC. The p85 subunit was co- immuno- precipitated with PTEN and migrates in parallel to PAC fractions both in the cytoplasm and the nucleus gel filtration, an observation which is consistent with our previous conclusion that there may be a single complex that can shuttle between the two compartments and that the same complex might migrate to the membrance where the PTEN substrate is localized.