Anaphase-Promoting Complex/Cyclosome Participates in the Acute Response to Protein-Damaging Stress

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Ahlskog JK, Björk JK, Elsing AN, Aspelin C, Kallio M, Roos-Mattjus P, Sistonen L
Publisher: AMER SOC MICROBIOLOGY
Publication year: 2010
Journal: Molecular and Cellular Biology
Journal acronym: MOL CELL BIOL
Volume number: 30
Issue number: 24
Start page: 5608
End page: 5620
Number of pages: 13
ISSN: 0270-7306
eISSN: 1098-5549


Abstract

The ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) drives degradation of cell cycle regulators in cycling cells by associating with the coactivators Cdc20 and Cdh1. Although a plethora of APC/C substrates have been identified, only a few transcriptional regulators are described as direct targets of APC/C-dependent ubiquitination. Here we show that APC/C, through substrate recognition by both Cdc20 and Cdh1, mediates ubiquitination and degradation of heat shock factor 2 (HSF2), a transcription factor that binds to the Hsp70 promoter. The interaction between HSF2 and the APC/C subunit Cdc27 and coactivator Cdc20 is enhanced by moderate heat stress, and the degradation of HSF2 is induced during the acute phase of the heat shock response, leading to clearance of HSF2 from the Hsp70 promoter. Remarkably, Cdc20 and the proteasome 20S core alpha 2 subunit are recruited to the Hsp70 promoter in a heat shock-inducible manner. Moreover, the heat shock-induced expression of Hsp70 is increased when Cdc20 is silenced by a specific small interfering RNA (siRNA). Our results provide the first evidence for participation of APC/C in the acute response to protein-damaging stress.

Last updated on 2019-19-07 at 04:48