Chp (GTPase)

Chp, also known as Cdc42-interacting protein 4 (CIP4) homology protein, is a member of a family of proteins that function as GTPase-activating proteins (GAPs) for Rho family GTPases, primarily Cdc42 and Rac. GAPs accelerate the intrinsic GTP hydrolysis rate of these small GTPases, thereby inactivating them.

Chp proteins contain a BAR (Bin/Amphiphysin/Rvs) domain, a GTPase-activating protein (GAP) domain, a pleckstrin homology (PH) domain, and a Src homology 3 (SH3) domain-binding region. The BAR domain is responsible for membrane binding and curvature sensing, influencing cellular processes such as endocytosis, exocytosis, and membrane trafficking. The GAP domain specifically interacts with and promotes the inactivation of Rho family GTPases. The PH domain binds to phosphoinositides, further modulating membrane association and protein localization. The SH3 domain-binding region allows for interaction with other proteins containing SH3 domains, enabling the formation of protein complexes and the regulation of downstream signaling pathways.

Chp proteins are implicated in a variety of cellular functions, including:

• Actin cytoskeleton regulation: By modulating the activity of Cdc42 and Rac, Chp proteins influence the organization and dynamics of the actin cytoskeleton, which is crucial for cell motility, adhesion, and morphogenesis.
• Membrane trafficking and endocytosis: The BAR domain-mediated membrane interaction and curvature sensing contribute to the regulation of vesicle formation and trafficking, particularly during endocytosis.
• Cell signaling: Through interactions with other signaling proteins via the SH3 domain-binding region, Chp proteins participate in various signaling pathways involved in cell growth, differentiation, and survival.

Dysregulation of Chp protein function has been implicated in several diseases, including cancer. Aberrant expression or activity of Chp proteins can disrupt cellular processes, leading to uncontrolled cell proliferation, metastasis, and other hallmarks of cancer. Research is ongoing to further elucidate the precise roles of Chp proteins in normal cellular physiology and disease pathogenesis, with the aim of developing novel therapeutic strategies targeting these proteins.