Dedicator of cytokinesis 1 (DOCK1) (DOCK1)

Dedicator of cytokinesis 1 (DOCK1), also known as DOCK180, is a major guanine nucleotide exchange factor (GEF) that specifically activates the small GTPase Rac1 (UniProt: Q14185). It plays a critical role in regulating the actin cytoskeleton, which is essential for processes such as cell migration, morphology changes, and phagocytosis of apoptotic cells (PubMed: 11544175). In the context of oncology, DOCK1 is frequently overexpressed and associated with increased tumor cell invasion and metastasis, particularly in glioblastoma and breast cancer (PubMed: 29765154). By facilitating the transition of Rac1 from an inactive GDP-bound state to an active GTP-bound state, DOCK1 promotes signaling pathways that drive cellular motility. Therapeutic strategies targeting DOCK1 include small molecule inhibitors like CPYPP that block its interaction with Rac1 and RNA-based approaches, such as siRNA or antisense oligonucleotides, designed to reduce DOCK1 mRNA levels (PubMed: 24561518). While promising for inhibiting metastasis, targeting DOCK1 may pose challenges related to its physiological roles in normal tissue remodeling and immune response.

Other names

DOCK180ced-5Dedicator of cytokinesis protein 1

Inhibition of Rac1 activation by blocking the guanine nucleotide exchange factor activity of DOCK1 or reducing DOCK1 protein levels through mRNA degradation.