PEST sequences mediate heat shock factor 2 turnover by interacting with the Cul3 subunit of the Cul3-RING ubiquitin ligase

Hongyan Xing, Yiling Hong, Kevin D. Sarge

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Cullin-RING ubiquitin ligases promote the polyubiquitination and degradation of many important cellular proteins, which previous studies indicated can be targeted for degradation via interaction with BTB domain-containing subunits of this E3 ligase complex. PEST domains are known to promote the degradation of proteins that contain them. However, the molecular mechanism by which PEST sequences promote degradation of these proteins is not understood. Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2. These results indicate how, at the molecular level, PEST sequences can promote the proteolysis of proteins that contain them. They also expand understanding of the mechanisms by which substrates can be recruited to Cullin-RING E3 ubiquitin ligases to include interactions between PEST sequences and Cul3.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalCell Stress and Chaperones
Volume15
Issue number3
DOIs
StatePublished - May 2010

Bibliographical note

Funding Information:
Acknowledgments We are grateful to Dr. Jeffrey Singer for his gift of the Cul3+/+ and Cul3+/− MEF cells, to Dr. Yue Xiong for providing anti-Cul3 antibodies, and to other members of the laboratory for comments. This research was supported by NIH grant GM64606 to K.D.S.

Funding

Acknowledgments We are grateful to Dr. Jeffrey Singer for his gift of the Cul3+/+ and Cul3+/− MEF cells, to Dr. Yue Xiong for providing anti-Cul3 antibodies, and to other members of the laboratory for comments. This research was supported by NIH grant GM64606 to K.D.S.

FundersFunder number
National Institutes of Health (NIH)
National Institute of General Medical SciencesR01GM064606
National Institute of General Medical Sciences

    Keywords

    • Cul3
    • HSF2
    • PEST
    • Protein turnover
    • Ubiquitin

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology

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