Abstract
Cytokinesis is the final step of cell division. Increasing evidence suggests failure of cytokinesis might contribute to the development of cancer. Here, we demonstrate that the serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13, a protein tyrosine phosphatase known to be involved in the regulation of cytokinesis, carcinogenesis and tumor aggressiveness. We show that SDCCAG3 is a novel endosomal protein, primarily localized at the early/recycling endosomal compartment. SDCCAG3 undergoes dynamic localization during cell division with strong accumulation at the midbody during cytokinesis. Overexpression as well as downregulation correlates with the generation of multinucleate cells. Furthermore, we show interaction of SDCCAG3 with the Arf GTPase activating protein GIT1 (G protein-coupled receptor kinase interactor-1). Overexpression of an ArfGAP-negative version of GIT1 also results in an increased number of multinucleate cells suggesting regulation of Arf-mediated vesicular trafficking or signaling via SDCCAG3. Finally, we demonstrate that SDCCAG3 expression levels are elevated in colon cancers. In summary, we have established SDCCAG3 as a novel endosomal protein, which is involved in the regulation of cytokinesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Adenocarcinoma / chemistry
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / metabolism*
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Antigens, Neoplasm / physiology
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Binding Sites
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line
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Colonic Neoplasms / chemistry
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Cytokinesis / physiology*
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Endosomes / chemistry
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Gene Expression Regulation, Neoplastic
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Giant Cells / pathology
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Humans
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Intracellular Signaling Peptides and Proteins
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Mice
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasm Proteins / physiology
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Protein Interaction Mapping
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Protein Structure, Tertiary
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Protein Tyrosine Phosphatase, Non-Receptor Type 13 / metabolism*
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RNA, Small Interfering / pharmacology
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Recombinant Fusion Proteins / metabolism
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Transport Vesicles / physiology
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Two-Hybrid System Techniques
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Vesicular Transport Proteins / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Neoplasm
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Cell Cycle Proteins
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ENTR1 protein, human
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GIT1 protein, human
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Intracellular Signaling Peptides and Proteins
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Neoplasm Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Vesicular Transport Proteins
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Protein Tyrosine Phosphatase, Non-Receptor Type 13
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Ptpn13 protein, mouse