4.7 Article

PDCD4 limits prooncogenic neuregulin-ErbB signaling

期刊

CELLULAR AND MOLECULAR LIFE SCIENCES
卷 78, 期 4, 页码 1799-1815

出版社

SPRINGER BASEL AG
DOI: 10.1007/s00018-020-03617-5

关键词

Neuregulin; ErbB receptors; Breast cancer; PDCD4

资金

  1. Instituto de Salud Carlos III through a Miguel Servet program [CP12/03073, CPII17/00015, PI15/00684, PI18/00796]
  2. Fundacion Samuel Solorzano Barruso [FS/19-2014]
  3. Junta de Castilla y Leon [BIO/SA28/13]
  4. Ministry of Economy and Competitiveness of Spain [BFU2015-71371-R]
  5. Instituto de Salud Carlos III through CIBERONC
  6. Scientific Foundation of the Spanish Association Against Cancer (AECC)
  7. ALMOM
  8. UCCTA
  9. CRIS Cancer Foundation
  10. European Community through the Regional Development Funding Program (FEDER)

向作者/读者索取更多资源

Neuregulins and their ErbB/HER receptors are important in mammalian development and tissue homeostasis, with PDCD4 identified as a novel mediator in neuregulin-ErbB signaling. Phosphorylation of PDCD4 at serine 67 is shown to promote its degradation and regulate important biological functions of neuregulin, such as proliferation, migration, and invasion, through mTORC1 and ERK1/2 pathways.
The neuregulins and their ErbB/HER receptors play essential roles in mammalian development and tissue homeostasis. In addition, deregulation of their function has been linked to the pathogenesis of diseases such as cancer or schizophrenia. These circumstances have stimulated research into the biology of this ligand-receptor system. Here we show the identification of programmed cell death protein-4 (PDCD4) as a novel neuregulin-ErbB signaling mediator. Phosphoproteomic analyses identified PDCD4 as protein whose phosphorylation increased in cells treated with neuregulin. Mutagenesis experiments defined serine 67 of PDCD4 as a site whose phosphorylation increased upon activation of neuregulin receptors. Phosphorylation of that site promoted degradation of PDCD4 by the proteasome, which depended on exit of PDCD4 from the nucleus to the cytosol. Mechanistic studies defined mTORC1 and ERK1/2 as routes implicated in neuregulin-induced serine 67 phosphorylation and PDCD4 degradation. Functionally, PDCD4 regulated several important biological functions of neuregulin, such as proliferation, migration, or invasion.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据