title: Wnt signaling stabilizes the DIXDC1 protein through decreased ubiquitin-dependent degradation.
abstract: Wnt signaling plays key roles in development, cell growth, differentiation, polarity formation, neural development, and carcinogenesis. DIX Domain Containing 1 (DIXDC1), a novel component of the Wnt pathway, was recently cloned. DIXDC1 is the human homolog of Ccd1, a positive regulator of the Wnt signaling pathway during zebrafish neural patterning. Little has been known about DIXDC1 gene expression regulation. In the present study, we showed that the DIXDC1 protein was induced upon Wnt-3a stimulation, whereas the DIXDC1 mRNA level was not significantly increased after Wnt-3a treatment. Positive DIXDC1 staining was detected in colon cancer cells and was colocalized with beta-catenin staining. However, the DIXDC1 mRNA expression decreased in human colon cancer cells compared to the matched normal colon epithelial cells. Our further investigation showed that the DIXDC1 protein was degraded through the proteasome pathway, and the activation of canonical Wnt signaling decreased the ubiquitin-dependent degradation of both the ectopic and endogenous DIXDC1 protein. In order to explore the possible mechanism of the ubiquitination of DIXDC1, we found that the phosphorylation of DIXDC1 was inhibited by Wnt-3a. Collectively, these results indicate that canonical Wnt/beta-catenin pathway activation might upregulate DIXDC1 through a post-translational mechanism by inhibiting the ubiquitin-mediated degradation of the DIXDC1 protein.
authors.affiliation: Department of Pathology, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Tengfang
authors.initials: T
authors.lastname: Zhu
authors.forename: Hongguang
authors.initials: H
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
mesh_terms: D003513:Cycloheximide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*; D051153:Wnt Proteins / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: C513335:DIXDC1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D003513:Cycloheximide