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The SUMO pathway is required for selective degradation of DNA topoisomerase IIβ induced by a catalytic inhibitor ICRF‐193 1
Author(s) -
Isik Sevim,
Sano Kuniaki,
Tsutsui Kimiko,
Seki Masayuki,
Enomoto Takemi,
Saitoh Hisato,
Tsutsui Ken
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00637-9
Subject(s) - topoisomerase , sumo protein , proteasome , ubiquitin , dna damage , dna , enzyme , biochemistry , gene isoform , immunoprecipitation , biology , microbiology and biotechnology , chemistry , gene
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.