Mutant screening for oncogenes of Ewing's sarcoma using yeast

Verfasser / Beitragende:
[Takao Kitagawa, Hajime Okita, Byron Baron, Kazuhiro Tokuda, Mikiko Nakamura, Yufeng Wang, Junko Akada, Hisashi Hoshida, Rinji Akada, Yasuhiro Kuramitsu, Kazuyuki Nakamura]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/16(2015-08-01), 6737-6744
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6621-2  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6621-2 
245 0 0 |a Mutant screening for oncogenes of Ewing's sarcoma using yeast  |h [Elektronische Daten]  |c [Takao Kitagawa, Hajime Okita, Byron Baron, Kazuhiro Tokuda, Mikiko Nakamura, Yufeng Wang, Junko Akada, Hisashi Hoshida, Rinji Akada, Yasuhiro Kuramitsu, Kazuyuki Nakamura] 
520 3 |a Many fusion genes, which are the result of chromosomal translocation and work as an oncogene, have been recently identified, but their mode of actions is still unclear. Here, we performed a yeast mutant screening for oncogenes of Ewing's sarcoma to easily identify essential regions responsible for fusion protein functions using a yeast genetic system. Three kinds of oncogenes including EWS/FLI1, EWS/ERG, and EWS/E1AF exhibited growth inhibition in yeast. In this screening, we identified 13 single amino acid substitution mutants which could suppress growth inhibition by oncogenes. All of the point mutation positions of the EWS/ETS family proteins were located within the ETS domain, which is responsible for the interaction with a specific DNA motif. Eight-mutated residues within the ETS domain matched to 13 completely conserved amino acid residues in the human ETS domains. Moreover, mutants also showed reduced transcriptional activities on the DKK2 promoter, which is upregulated by the EWS/ETS family, compared to that of the wild type. These results suggest that the ETS domain in the EWS/ETS family proteins may be a primary target for growth inhibition of Ewing's sarcoma and that this yeast screening system can be applied for the functional screening of the oncogenes. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Ewing's sarcoma  |2 nationallicence 
690 7 |a EWS/ETS family  |2 nationallicence 
690 7 |a ETS domain  |2 nationallicence 
690 7 |a Yeast  |2 nationallicence 
700 1 |a Kitagawa  |D Takao  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Okita  |D Hajime  |u Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya-ku, 157-8535, Tokyo, Japan  |4 aut 
700 1 |a Baron  |D Byron  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Tokuda  |D Kazuhiro  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Nakamura  |D Mikiko  |u Innovative center, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
700 1 |a Wang  |D Yufeng  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Akada  |D Junko  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Hoshida  |D Hisashi  |u Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
700 1 |a Akada  |D Rinji  |u Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
700 1 |a Kuramitsu  |D Yasuhiro  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
700 1 |a Nakamura  |D Kazuyuki  |u Center of Clinical Laboratories in Tokuyama Medical Association Hospital, 745-0846, Shunan, Japan  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/16(2015-08-01), 6737-6744  |x 0175-7598  |q 99:16<6737  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6621-2  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6621-2  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kitagawa  |D Takao  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Okita  |D Hajime  |u Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya-ku, 157-8535, Tokyo, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Baron  |D Byron  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tokuda  |D Kazuhiro  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Nakamura  |D Mikiko  |u Innovative center, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Yufeng  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Akada  |D Junko  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hoshida  |D Hisashi  |u Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Akada  |D Rinji  |u Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Tokiwadai, 755-8611, Ube, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kuramitsu  |D Yasuhiro  |u Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Nakamura  |D Kazuyuki  |u Center of Clinical Laboratories in Tokuyama Medical Association Hospital, 745-0846, Shunan, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/16(2015-08-01), 6737-6744  |x 0175-7598  |q 99:16<6737  |1 2015  |2 99  |o 253