Metastasis-associated NDPK-A is involved in translation via eEF1Bα
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 t...
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ndltd-TW-099NCKU55380042015-10-30T04:05:21Z http://ndltd.ncl.edu.tw/handle/78473285712054099053 Metastasis-associated NDPK-A is involved in translation via eEF1Bα 癌症轉移相關的NDPK-A藉由eEF1Bα參與在轉譯作用中 Renn-ShiuanWei 魏任宣 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. Christina Lin Chang 張玲 2011 學位論文 ; thesis 112 en_US |
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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.
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author2 |
Christina Lin Chang |
author_facet |
Christina Lin Chang Renn-ShiuanWei 魏任宣 |
author |
Renn-ShiuanWei 魏任宣 |
spellingShingle |
Renn-ShiuanWei 魏任宣 Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
author_sort |
Renn-ShiuanWei |
title |
Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
title_short |
Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
title_full |
Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
title_fullStr |
Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
title_full_unstemmed |
Metastasis-associated NDPK-A is involved in translation via eEF1Bα |
title_sort |
metastasis-associated ndpk-a is involved in translation via eef1bα |
publishDate |
2011 |
url |
http://ndltd.ncl.edu.tw/handle/78473285712054099053 |
work_keys_str_mv |
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