The SUMO pathway is required for selective degradation of DNA topoisomerase IIβ induced by a catalytic inhibitor ICRF-193

Sevim Isik, Kuniaki Sano, Kimiko Tsutsui, Masayuki Seki, Takemi Enomoto, Hisato Saitoh, Ken Tsutsui

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)374-378
Number of pages5
JournalFEBS Letters
Volume546
Issue number2-3
DOIs
Publication statusPublished - Jul 10 2003

Fingerprint

Type II DNA Topoisomerase
Degradation
DNA Damage
Protein Isoforms
Enzymes
Ubiquitins
Polyubiquitin
Sumoylation
DNA
Type I DNA Topoisomerase
Poisons
Proteasome Endopeptidase Complex
Cells
Pharmaceutical Preparations
4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione

Keywords

  • DNA topoisomerase II
  • Proteasome
  • SUMO
  • Ubiquitin-like protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The SUMO pathway is required for selective degradation of DNA topoisomerase IIβ induced by a catalytic inhibitor ICRF-193. / Isik, Sevim; Sano, Kuniaki; Tsutsui, Kimiko; Seki, Masayuki; Enomoto, Takemi; Saitoh, Hisato; Tsutsui, Ken.

In: FEBS Letters, Vol. 546, No. 2-3, 10.07.2003, p. 374-378.

Research output: Contribution to journalArticle

Isik, Sevim ; Sano, Kuniaki ; Tsutsui, Kimiko ; Seki, Masayuki ; Enomoto, Takemi ; Saitoh, Hisato ; Tsutsui, Ken. / The SUMO pathway is required for selective degradation of DNA topoisomerase IIβ induced by a catalytic inhibitor ICRF-193. In: FEBS Letters. 2003 ; Vol. 546, No. 2-3. pp. 374-378.
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