title: Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1.
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.
authors.affiliation: Innovation Center Okayama for Nanobio-Targeted Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueki
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirata
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Haruki
authors.initials: H
authors.lastname: Kaku
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002460:Cell Line; D018925:Chemokines; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; C533376:DYNLT1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; D004398:Dyneins