NMR uncovers direct interaction between human NEDD4-1 and p34SEI−1

Pravesh Shrestha, Ji Hye Yun, Yoon Joo Ko, Kyu Jeong Yeon, Dooseop Kim, Heejong Lee, Dong Hoon Jin, Ki Yup Nam, Hye Dong Yoo, Weontae Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

PTEN, an important tumor suppressor and a key regulator of the PI3K/AKT signaling pathway, is often deleted/mutated in different types of cancer. The E3 ubiquitin ligase NEDD4-1 catalyzes the polyubiquitination of PTEN, thereby acting as a negative regulator of PTEN. Stability of NEDD4-1, in turn, is tightly controlled by a 34 kDa oncoprotein, p34SEI−1 and it regulates PTEN degradation and activates PI3K/AKT pathway, resulting in cancer metastasis. p34SEI−1 affects not only the expression of NEDD4-1 during transcription and translation but also the subcellular localization of PTEN. This emphasizes the need to understand, at molecular level, the interaction between NEDD4-1 and p34SEI−1. A recent study showed that NEDD4-1 interacts with p34SEI−1 via its WWI domain. However, a detailed interaction for molecular level is yet unknown. We report that the WW1 domain of NEDD4-1 recognizes the SERTA domain containing the proline rich region (PRR motif) in p34SEI−1. TALOS analysis based on NMR data confirms three conserved β-sheets in NEDD4-1 WW1 and the central β-sheet of NEDD4-1 WW1 plays a role for protein stability by the backbone dynamics experiments. NMR titration data revealed the binding site for p34SEI−1 with NEDD4-1. Our data will provide insights into the molecular mechanism of NEDD4-1 and p34SEI−1 interaction, which will be directly used for drug design which inhibits the molecular interaction involved in different cancer signaling.

Original languageEnglish
Pages (from-to)984-990
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume490
Issue number3
DOIs
Publication statusPublished - 2017 Aug 26

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Shrestha, P., Yun, J. H., Ko, Y. J., Yeon, K. J., Kim, D., Lee, H., Jin, D. H., Nam, K. Y., Yoo, H. D., & Lee, W. (2017). NMR uncovers direct interaction between human NEDD4-1 and p34SEI−1. Biochemical and Biophysical Research Communications, 490(3), 984-990. https://doi.org/10.1016/j.bbrc.2017.06.151