Rho GTPase-activating protein 8 (ARHGAP8)

Rho GTPase-activating protein 8 (ARHGAP8) is a multidomain enzyme of the RhoGAP family that modulates the activity of small Rho-type GTPases, primarily by converting them from an active (GTP-bound) to inactive (GDP-bound) state. It functions as a scaffolding protein synchronizing RhoA inactivation and Rac1 activation in a spatiotemporally coordinated manner to facilitate cell migration and invasion. ARHGAP8 influences Erk pathway activation and cell motility, and its altered expression has been linked to cancer, particularly as a potential tumor suppressor or prometastatic factor depending on context. The protein contains a BCH domain, proline-rich regions, and a central SH3-binding motif that interacts with actin regulators like cortactin. Its expression is found in various tissues, with notable roles in cancer where it can act as both a prognostic biomarker and a possible therapeutic checkpoint in EGFR-Vav1-Rac1-RhoA signaling axes. No drugs are currently known to directly target ARHGAP8, but its central role in cell motility and signal transduction makes it a relevant molecule for therapeutic research, especially in oncology.

Other names

ARHGAP8BPGAP1PP610FLJ20185Rho-type GTPase-activating protein 8BCH domain-containing Cdc42GAP-like proteinBNIP-2 and Cdc42GAP homology domain-containing, proline-rich and Cdc42GAP-like protein subtype-1

Drugs or interventions could potentially inhibit or modify ARHGAP8-dependent RhoA inactivation or Rac1 activation in cancer cell motility, but no direct ARHGAP8-targeting agents are reported