The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis

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.

Proximity Interactions among Centrosome Components Identify Regulators of Centriole Duplication

“…The PLK4 BioID hits also include proteins not previously implicated in centriole duplication. SDCCAG3, the highest non-PLK4 hit, localizes to the centrosome, endosomes, and the midbody during cytokinesis, and regulates cytokinesis [13]. …”

Genetic alterations of protein tyrosine phosphatases in human cancers

“…PTPN13 interacts with serologically defined colon cancer antigen-3 (SDCCAG3) and regulates cytokinesis. 113 Another PTPN13 substrate involved in cytokinesis is Valosin Containing Protein (VCP/p97). Dephosphorylation of VCP/p97 by PTPN13 affects its midbody localization during cytokinesis.…”

Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma membrane recycling

“…In addition to established interactors, including all components of the WASH complex, this has identified a number of new retromer accessory proteins that we have functionally validated in the context of retromer-mediated endosome-to-plasma-membrane recycling. These include ANKRD50, a multiple ankyrin-repeat domain containing protein with no described function; SDCCAG3, an endosome-associated protein implicated in cytokinesis ( Hagemann et al, 2013 ), and VARP (also known as ANKRD27), an endosome-associated effector for Rab32 and Rab38 that possesses guanine-nucleotide exchange activity against Rab21 ( Zhang et al, 2006 ) and traps the R-SNARE VAMP7 in a closed fusogenically inactive conformation and thereby regulates late endosome fusion with the lysosome ( Schäfer et al, 2012 ). Through comparative analysis of four functionally distinct SNX27–retromer cargos – the glucose transporter GLUT1 (also known as SLC2A1), the monocarboxylate transporter MCT1, the TNF-receptor super-family member TRAILR1 (also known as TNFRSF10A) and the adhesion receptor CD97 – we reveal underlying mechanistic heterogeneity in retromer-mediated endosome-to-plasma-membrane transport and provide a molecular framework to aid the further analysis of retromer function.…”