Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1

Kazuhiko Ochiai, Masami Watanabe, Hideo Ueki, Peng Huang, Yasuyuki Fujii, Yasutomo Nasu, Hirofumi Noguchi, Takeshi Hirata, Masakiyo Sakaguchi, Nam Ho Huh, Yuji Kashiwakura, Haruki Kaku, Hiromi Kumon

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

REIC/Dkk-3 is a member of the Dickkopf family proteins known as Wnt-antagonists, and REIC/Dkk-3 expression is downregulated in a broad range of cancer types. REIC/Dkk-3 acts as a tumor suppressor in multiple cancer cell lines by inducing apoptosis through endoplasmic reticulum (ER) stress signaling. However, the intracellular interaction partners of REIC/Dkk-3 have not been fully elucidated. By employing yeast two-hybrid screening, we identified the human dynein light chain, Tctex-1, as a novel interaction partner of REIC/Dkk-3. We further disclosed that the interaction involves the 136-157 amino acid region of REIC/Dkk-3 by using the mammalian two-hybrid system. Interestingly, this binding region of REIC/Dkk-3 with Tctex-1 contains an amino acid sequence motif [-E-X-G-R-R-X-H-] which was previously reported as the Tctex-1 binding domain of dynein intermediate chain (DIC). Immunocytochemistry demonstrated that both REIC/Dkk-3 and Tctex-1 were localized around the ER of human fibroblasts, and the similar distribution pattern of the proteins suggests that their interaction occurs around the ER. This is the first study showing the interaction of a Dickkopf family protein with a dynein motor complex protein. The link between REIC/Dkk-3 and Tctex-1 may be of significance for understanding the molecular functions of the proteins in ER stress signaling and intracellular dynein motor dynamics, respectively.

Original languageEnglish
Pages (from-to)391-395
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume412
Issue number2
DOIs
Publication statusPublished - Aug 26 2011

Keywords

  • Dkk-3
  • Dynein
  • Endoplasmic reticulum
  • REIC
  • Tctex-1
  • Two-hybrid screening

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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