Characterization of functional domains in NME1L regulation of NF-κB signaling

Dong Joo You, Cho Rong Park, Sunam Mander, Curie Ahn, Jae Young Seong, Jong-Ik Hwang

Research output: Contribution to journalArticle

Abstract

NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with IKKβ and regulating its activity. In the present study, we tried to define the role of the Nterminal 25 amino acids of NME1L in NF-κB activation signaling. Unfortunately, the sequence itself did not interact with IKKβ, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, IKKβ interaction and regulation of NF- ?B signaling. The inhibitory effect of the fragment on cancer cell migration and NF-κB-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and IKKβ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and IKKβ-related anti-cancer drug design.

Original languageEnglish
Pages (from-to)403-409
Number of pages7
JournalMolecules and Cells
Volume39
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Fingerprint

Amino Acids
Neoplasms
Drug Design
Alternative Splicing
Cell Movement
Down-Regulation
Neoplasm Metastasis
Gene Expression
Genes
Proteins
Direction compound

Keywords

  • Anti-metastasis
  • Dimerization
  • IKKβ
  • NF-κB
  • NME1L

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Cell Biology

Cite this

Characterization of functional domains in NME1L regulation of NF-κB signaling. / You, Dong Joo; Park, Cho Rong; Mander, Sunam; Ahn, Curie; Seong, Jae Young; Hwang, Jong-Ik.

In: Molecules and Cells, Vol. 39, No. 5, 01.05.2016, p. 403-409.

Research output: Contribution to journalArticle

You, Dong Joo ; Park, Cho Rong ; Mander, Sunam ; Ahn, Curie ; Seong, Jae Young ; Hwang, Jong-Ik. / Characterization of functional domains in NME1L regulation of NF-κB signaling. In: Molecules and Cells. 2016 ; Vol. 39, No. 5. pp. 403-409.
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