Rac1b

Rac1b is an alternatively spliced isoform of the small GTPase Rac1, generated by the insertion of 19 amino acids (exon 3b) adjacent to the switch II region. This modification confers constitutive activity due to accelerated GTP/GDP exchange and impaired GTP hydrolysis, decoupling Rac1b from normal regulatory mechanisms. Rac1b is overexpressed in various human cancers (including breast, colorectal, pancreas, lung, and thyroid), where it drives cell proliferation, cell survival, resistance to apoptosis, epithelial-mesenchymal transition, cell migration, invasion, and notably chemoresistance in cancer stem cells. While absent or low in most normal tissues, its upregulation correlates with worse patient outcomes in malignancy. Therapeutic efforts are in development to specifically target Rac1b function, but the current lack of selective drugs and the important physiological roles of its parent isoform Rac1 present significant challenges.

Other names

Ras-related C3 botulinum toxin substrate 1bRAC1B

Inhibition of Rac1b suppresses cancer cell proliferation, survival, and chemoresistance. Inhibition disrupts maintenance of cancer stem cells and overcomes resistance to agents like doxorubicin. Modulation of GTPase activity to trap Rac1b in inactive states may be a strategy under investigation.