Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

TBC1D3 was first described as an oncogene [63] and was also identified as PRC17 during the analysis of cells derived from prostate and breast cancer patients [64] . A predicted GAP activity of the TBC domain is equivocal. While a weak GAP activity was documented in one study [64] , this finding could not be confirmed by others; however, TBC1D3 is still thought to be involved in macropinocytosis [58] . TBC1D3 dysregulates the epidermal growth factor receptor signal transduction pathway and enhances cell proliferation [61] . Further studies showed that TBC1D3 protein is ubiquitinated and palmitoylated, and degradation of TBC1D3 protein is regulated by Cul7 [62, 65] . TBC1D3 genes were also shown to be involved in Insulin/IGF signaling [66] . Over-expression of TBC1D3 leads to an increase in cell proliferation in basal regions of the developing mouse cortex, as well as disruptions to adherens junctions and formation of column-like structures [67] . Similar results were also obtained in cultured human brain slices, where it was shown that TBC1D3 is critical for the generation of outer radial glial cells [67] . Finally, it was shown that TBC1D3 affects the migration of human breast cancer cells by regulating TNFα/NF-κB signaling [68] .