ECT2 BRCT domains (human, recombinant)

Epithelial cell-transforming sequence 2 oncogene (ECT2) is a guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP from small GTPases of the Rho family, such as RhoA, RhoC, Rac1, and Cdc42.¹ ECT2 GEF activity plays an essential role during cytokinesis.² ECT2 contains a DH (DBL-homology) domain, a pleckstrin homology (PH) domain and tandem BRCT domains.³ BRCT domains are modular units of ~100 amino acids that fold independently and recognize linear phosphoserine or phosphothreonine regions to mediate protein-protein and protein-DNA interactions.^4,5 BRCT domains were initially recognized in the C-terminal region of the breast cancer protein BRCA1, as well as the p53 binding protein and the yeast cell cycle checkpoint protein RAD9.⁶ BRCT domains often occur as tandem repeats at the C-terminal end of several proteins that are functionally diverse.⁵ Most BRCT domain-containing proteins participate in DNA-damage checkpoint control or DNA-repair pathways, or both.^7,6 The BRCT domains of ECT2 make intramolecular interactions with the C-terminal DH/PH domains of the protein, thus, masking the catalytic GEF activity for Rho GTPases.⁸ Additionally, release of the autoinhibition by the BRCT domains may be necessary for the proper functioning of ECT2 during cytokinesis.⁸ Expression levels of ECT have been shown to be strongly correlated with prognosis in glioma patients.⁹

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1. Miki, T., Smith, C.L., Long, J.E., et al. Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature 362(6419), 462-465 (1993).

2. Kimura, K., Tsuji, T., Takada, Y., et al. Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation. The Journal of Biological Chemisty 275(23), 17233-17236 (2000).

3. Fields, A.P., and Justilien, V. The guanine nucleotide exchange factor (GEF) Ect2 is an oncogene in human cancer. Adv. Enzyme Regul. 50(1), 190-200 (2010).

4. Manke, I.A., Lowery, D.M., Nguyen, A., et al. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302(5645), 636-639 (2003).

5. Woods, N.T., Mesquita, R.D., Sweet, M., et al. Charting the landscape of tandem BRCT domain-mediated protein interactions. Sci. Signal. 5(242), rs6 (2012).

6. Bork, P., Hofmann, K., Bucher, P., et al. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. The FASEB Journal 11(1), 68-76 (1997).

7. Callebaut, I., and Mornon, J.P. From BRCA1 to RAP1: A widespread BRCT module closely associated with DNA repair. FEBS Lett. 400(1), 25-30 (1997).

8. Kim, J.E., Billadeau, D.D., and Chen, J. The tandem BRCT domains of ect2 are required for both negative and positive regulation of ect2 in cytokinesis. The Journal of Biological Chemisty 280(7), 55733-55739 (2005).

9. Sano, M., Genkai, N., Yajima, N., et al. Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients. Oncol. Rep. 16(5), 1093-1098 (2006).