More About GBP1
The guanine nucleotide-binding protein 1 (GBP1; EC 3.6.5.6) is one of the 7 members of the large GTPase family and most strongly induced by interferons. Members of this family share the ability to undergo oligomerization with a high-turnover GTPase activity. Structural hallmarks of GBP1 are a large globular α/β-domain harboring the GTPase activity, and an elongated C-terminal part organized in an α-helical structure with unique features[1]. GBP1 is highly expressed in endothelial cells, and is activated by inflammatory cytokines in vitro and in vivo[2]. The functional role of GBP1 has not been fully elucidated to date, but it was shown to inhibit the invasiveness and tube-forming capability of endothelial cells, play a role in cell-autonomous immunity and bacterial infection, and to exhibit antiviral properties. Since GBP1 is also known to interact with βIII-tubulin, where it operates as a crucial element to incorporate pro-survival kinases such as PIM1 and NEK6 into microtubules, and seems to be involved in the drug resistance to paclitaxel, it is of interest for the development of a new class of anticancer agents against Paclitaxel resistant cancer cells[3].
[1] E. Guenzi et al. The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression. EMBO J. 2003 Aug 1;22(15):3772-82.
[2] M. Fukumoto et al. Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance. Cancer Sci. 2014 Oct;105(10):1351-9.
[3] M. Andreoli et al. Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. J Med Chem. 2014 Oct 9;57(19):7916-32.