Dedicator of cytokinesis protein 1 (DOCK1) (DOCK1)

Dedicator of cytokinesis protein 1 (DOCK1), also known as DOCK180, is a major guanine nucleotide exchange factor (GEF) specifically for the Rho GTPase Rac1 (UniProt: Q14185). It functions primarily through its conserved DOCK homology region 2 (DHR-2) domain, which catalyzes the exchange of GDP for GTP on Rac1, thereby triggering downstream signaling pathways involved in actin cytoskeleton remodeling and cell motility (PubMed: 12150907). DOCK1 is frequently overexpressed or hyperactivated in various cancers, such as glioblastoma and breast cancer, where it promotes tumor cell invasion and metastasis (PubMed: 23434374). It often works in a bipartite complex with the adaptor protein ELMO1 to achieve maximal GEF activity. Beyond oncology, DOCK1 plays critical roles in physiological processes such as the engulfment of apoptotic cells and cardiovascular development. Therapeutic strategies targeting the DOCK1 DHR-2 domain aim to disrupt its interaction with Rac1, offering a potential avenue to inhibit metastatic progression (PubMed: 26063802). Small molecule inhibitors like TBOPP have demonstrated the feasibility of targeting this domain to reduce cancer cell migration in preclinical models.

Other names

DOCK180180 kDa protein downstream of CRKCED5DOCK1 DHR-2 domain

Inhibition of the DHR-2 domain-mediated guanine nucleotide exchange on Rac1 GTPase