2010 Fiscal Year Final Research Report
SUMOylation is involved in the degradation of DNA topoisomerase IIβ induced by antitumor drug treatment
| Project/Area Number |
21791362
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Okayama University |
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Principal Investigator |
SANO Kuniaki Okayama University, 大学院・医歯薬学総合研究科, 助教 (00294405)
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| Project Period (FY) |
2009 – 2010
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| Keywords | DNAトポイソメラーゼII / 抗がん剤 / エトポシド / クランプ形成 / 二本鎖DNA切断 / タンパク質分解 / SUMO化 / ユビキチン化 |
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| Research Abstract |
Degradation of DNA topoisomerase II (Topo II) was induced by Topo II inhibitors. The lysine residue at amino acid position 1259 of Topo IIβ was modified by SUMO-2/3 in advance of the degradation. The lysine-to-arginine substitution (K1259R), which was not modified by SUMO, prevented the degradation following its inhibition. On the other hand, the same drugs did not induce the degradation of Topo IIα although its activity was inhibited similarly. Over-expression experiments and analysis of SUMOylation sites suggested that the difference in their fate after inhibition depends on the presence or absence of SUMOylation site, not on the expression timing or nuclear localization.
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