Metastasis-associated NDPK-A is involved in translation via eEF1Bα

• Main Authors: Renn-ShiuanWei, 魏任宣
• Other Authors: Christina Lin Chang
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/78473285712054099053

碩士 === 國立成功大學 === 分子醫學研究所 === 99 === Metastasis is a major cause of death in cancer patients, however, its molecular mechanism remain largely unclear. The nm23-H1 gene encoding nucleotide diphosphate kinase A (NDPK-A) was first discovered as a metastasis-associated gene. Our lab further identified the S120G mutation in patients with advanced neuroblastoma. To understand the molecular mechanism of NDPK-A in tumor metastasis, we have found that NDPK-A interacted with a translation elongation factor, namely eEF1Bα, by yeast two-hybrid system and immunoprecipitation. In this thesis, a nickel pull-down assay also confirmed such an interaction. In an in-vivo dual-luciferase reporter system, NDPK-A and its S120G mutant (NDPK-AS120G) increased cap-dependent translation by 1.5 and 2 folds respectively. Moreover, NDPK-AS120G but not wild type NDPK-A enhanced IRES-dependent translation by 1.5 folds. However, an enzymatically inactive NDPK-AH118F did not show detectable effect on translation efficiency. NDPK-AS120G also increased new protein synthesis, while retaining translation during early period of serum starvation. Overall, NDPK-AS120G was more effective than its wild type in enhancing translation, and the phosphotransferase activity was required for NDPK-A mediated translation. Our findings suggest a novel link between tumor metastasis and translation control.