Efp targets 14-3-3σ for proteolysis and promotes breast tumour growth

Tomohiko Urano, Tomoyuki Saito, Tohru Tsukui, Masayo Fujita, Takayuki Hosoi, Masami Muramatsu, Yasuyoshi Ouchi and Satoshi Inoue ()
Additional contact information
Tomohiko Urano: The University of Tokyo
Tomoyuki Saito: The University of Tokyo
Tohru Tsukui: Saitama Medical School
Masayo Fujita: The University of Tokyo
Takayuki Hosoi: The University of Tokyo
Masami Muramatsu: Saitama Medical School
Yasuyoshi Ouchi: The University of Tokyo
Satoshi Inoue: The University of Tokyo

Nature, 2002, vol. 417, issue 6891, 871-875

Abstract: Abstract Oestrogen exerts its influence on target organs through activating oestrogen receptors (ERs) and regulating downstream genes by means of their oestrogen-responsive elements. Efp, a target gene product of ERα1,2,3, is a member of the RING-finger B-box coiled-coil (RBCC) motif family4. Efp is predominantly expressed in various female organs2 as well as in breast cancers5, and is thought to be essential for oestrogen-dependent cell proliferation and organ development—Efp-disrupted mice display underdeveloped uteri and reduced oestrogen responsiveness6. Here we show that Efp is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3σ, a negative cell cycle regulator that causes G2 arrest7. We demonstrate that tumour growth of breast cancer MCF7 cells implanted in female athymic mice is reduced by treatment with antisense Efp oligonucleotide. Efp-overexpressing MCF7 cells in ovariectomized athymic mice generate tumours in the absence of oestrogen. Loss of Efp function in mouse embryonic fibroblasts results in an accumulation of 14-3-3σ, which is responsible for reduced cell growth. These data provide an insight into the cell-cycle machinery and tumorigenesis of breast cancer by identifying 14-3-3σ as a target for proteolysis by Efp, leading to cell proliferation.

Date: 2002
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature00826 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:417:y:2002:i:6891:d:10.1038_nature00826

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature00826

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().