The SUMO pathway is required for selective degradation of DNA topoisomerase IIβ induced by a catalytic inhibitor ICRF‐1931

FEBS Letters

Enomoto, Takemi⁴  Tsutsui, Ken¹  Saitoh, Hisato²  Seki, Masayuki⁴  Isik, Sevim¹  Tsutsui, Kimiko³  Sano, Kuniaki³ 

[1] Department of Molecular Biology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan;Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan;Department of Neuroanatomy and Neurobiology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan;Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan

关键词: Ubiquitin-like protein;    SUMO;    DNA topoisomerase II;    Proteasome;    SUMO;    small ubiquitin-like modifier;    topo I/II;    DNA topoisomerase I/II;    PAGE;    polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(03)00637-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

DNA topoisomerase I and II have been shown to be modified with a ubiquitin-like protein SUMO in response to their specific inhibitors called ‘poisons’. These drugs also damage DNA by stabilizing the enzyme–DNA cleavable complex and induce a degradation of the enzymes through the 26S proteasome system. A plausible link between sumoylation and degradation has not yet been elucidated. We demonstrate here that topoisomerase IIβ, but not its isoform IIα, is selectively degraded through proteasome by exposure to the catalytic inhibitor ICRF-193 which does not damage DNA. The β isoform immunoprecipitated from ICRF-treated cells was modified by multiple modifiers, SUMO-2/3, SUMO-1, and polyubiquitin. When the SUMO conjugating enzyme Ubc9 was conditionally knocked out, the ICRF-induced degradation of topoisomerase IIβ did not occur, suggesting that the SUMO modification pathway is essential for the degradation.

【 授权许可】

Unknown