The Mechanism Of PHLPP Action In Tumor

PHLPP1 and PHLPP2 phosphatases exert theirtumor-suppressing functions by dephosphorylation and inactivation of Akt in several breast cancer and glioblastoma cells. However, Akt, or other known targets of PHLPPs that include PKC and ERK, may not fully elucidate the physiological role of the multifunctional phosphatases, especially their powerful apoptosis induction function. Here, we show that PHLPPs induce apoptosis in cancer cells independent of the known targets of PHLPPs. We identified Mst1 as a binding partner that interacts with PHLPPs both in vivo and in vitro. PHLPPs dephosphorylate Mstl on the T387 inhibitory site, which activate Mstl and its downstream effectors p38 and JNK to induce apoptosis. The same T387 site can be phosphorylated by Akt. Thus, PHLPP, Akt, and Mstl constitute an autoinhibitory triangle that controls the fine balance of apoptosis and proliferation that is cell type and context dependent. Secondly, we show that the transcription of PHLPP was influenced by the binding between PHLPPpromoter and C/EBPs.their interactions regulate the expression of PHLPP and then effect the growth, metastasis and apoptosis of cancer cell.At last, The route of synthesis reported was optimized, we got the activity-based probe for phosphatase easily, and checked some of it's reactions. We tested its specificity with some phosphatases, and studied its functions with cancer cells and tumoer tissue sample. Valuable exploration has been performed for the following experiments such as immunoprecipitation and mass spectra. Our data demonstrate that properly Activity-based protein profiling should be studied in cancer.