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Arsenic trioxide stimulates SUMO‐2/3 modification leading to RNF4‐dependent proteolytic targeting of PML
Author(s) -
Weisshaar Stefan R.,
Keusekotten Kirstin,
Krause Anke,
Horst Christiane,
Springer Helen M.,
Göttsche Kerstin,
Dohmen R. Jürgen,
Praefcke Gerrit J.K.
Publication year - 2008
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/j.febslet.2008.08.008
Subject(s) - arsenic trioxide , rnf4 , sumo protein , ubiquitin , ubiquitin ligase , promyelocytic leukemia protein , chemistry , in vivo , acute promyelocytic leukemia , in vitro , microbiology and biotechnology , biochemistry , biology , apoptosis , transcription factor , zinc finger , genetics , gene , retinoic acid
We have recently reported that poly‐SUMO‐2/3 conjugates are subject to a ubiquitin‐dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO‐2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo . The SUMO‐binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Reconstitution of SUMO‐dependent ubiquitylation of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4.