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

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• 作者：Kazuhiko Ochiai^a ;   ; ^f ; Masami Watanabe^a ;   ; ^b ;   ; ^c ;   ; ^{mwcorrespondence@gmail.com} ; Hideo Ueki^c ; Peng Huang^a ;   ; ^b ; Yasuyuki Fujii^a ; Yasutomo Nasu^c ; Hirofumi Noguchi^d ; Takeshi Hirata^c ; Masakiyo Sakaguchi^e ; Nam-ho Huh^e ; Yuji Kashiwakura^a ; Haruki Kaku^a ;   ; ^b ;   ; ^c ; Hiromi Kumon^a ;   ; ^b ;   ; ^c
• 关键词：REIC ; Dkk-3 ; Tctex-1 ; Dynein ; Endoplasmic reticulum ; Two-hybrid screening
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：26 August 2011
• 年：2011
• 卷：412
• 期：2
• 页码：391-395
• 全文大小：550 K

文摘

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?57 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.