Figure 2.

Overview of GBP1 function. GBP1 may be upregulated in response to interferons or other inflammatory cytokines, such as TNFα, and is downregulated by growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor β (TGFβ). GBP1 may localize cytosolically, at membrane surfaces, or extracellularly via secretion. GBP1 self-assembly and binding partner accessibility are regulated by its GTP binding status, where GTP favors assembly while GDP inhibits it. GBP1 has been found in complex with TUBB3 (β tubulin III), PIM1 (Pim-1 proto-oncogene, serine/threonine kinase), ATG8 (autophagy-related protein 8), p62 (sequestosome 1), F-actin monomers, and others, which facilitates its diverse cellular effects. These include an essential role in the clearance of intracellular pathogens, arrest of cell proliferation in inflammatory conditions, and protection of cells from inflammation-induced apoptosis. These activities may be hijacked by upstream oncogenic events to promote cancer cell survival against cytotoxic therapies, such as paclitaxel and radiation therapy. Other functions of GBP1, such as modulation of inflammatory state, its association with factors such as PIM1, and promotion of cell-cell adhesion dysregulation may serve to increase disease progression in diverse cancer sub-types, including ovarian, head-and-neck, and brain lesions. In human patients, mutations in GBP1 are associated with chronic viral infection, although mutation in GBP1 is not necessary for its involvement in treatment resistance.