| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 104 === Trim37 was first known from Mulibrey nanism (muscle-liver-brain-eye nanism, MUL) which is caused by mutations at chromosome 17q22-23 where Trim37 gene located. Except Mulibrey nanism, recent studies indicate the association between Trim37 and cancer. Trim37 gene amplification was observed in ovarian cancer and breast cancer, and breast cancer patients who expressed high Trim37 were with poor survival rates. The latest research showed that Trim37 is an onco-protein of breast cancer and promotes tumor growth.
Based on published studies, we hypothesize that Trim37 expression level is important for tumorigenesis. However the regulation of Trim37 expression level was not well-understood. In our research, we aim to identify the mechanism of regulation for Trim37 expression level and the correlation between Trim37 and breast cancer. In our previous data, we knew that Trim37 is a phosphoprotein. Here, we used Phos-tag and colony formation assay to show that Trim37 is phosphorylated at S461 residue, which and is important for protein stability of Trim37 and colony formation. Furthermore, we exam the role of the phosphatase PP2A, a candidate of Trim37-interacting protein from GST-pull down assay. By using Co-immunoprecipitation assay, we showed that protein phosphatase 2A (PP2A) interacts with Trim37. After treat cycloheximide to inhibit protein synthesis, we observed that PP2A downregulated Trim37 protein stability and expression level. Moreover, colony formation was reduced in PP2A-overexpressed MCF-7 cells. However, S461D Trim37 expressed-MCF-7 cells were not affected by PP2A. Because PP2A is a well-known tumor suppressor, our data indicates that the suppression of tumor growth by PP2A partially through decreasing Trim37 protein stability, that leads to reduction of Trim37 expression level and decrease of the colony formation ability in breast cancer cells MCF-7
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