Cofilin-1 (CFL1) (CFL1)

Cofilin-1 is a ubiquitous actin-binding protein essential for the regulation of actin filament dynamics through its severing and depolymerizing activities (UniProt: P23528). The activity of Cofilin-1 is critically regulated by a phosphorylation-dephosphorylation cycle at its Serine-3 residue; phosphorylation by LIM kinases (LIMK1/2) or TES kinases (TESK1/2) renders the protein inactive, preventing it from binding to actin (PubMed: 15659503). Conversely, dephosphorylation by phosphatases such as Slingshot (SSH) or Chronophin (CIN) restores its actin-remodeling function. In oncology, overexpressed or hyperactive Cofilin-1 is associated with increased cell motility, invasion, and metastasis (PubMed: 20473360). In neurodegenerative diseases, particularly Alzheimer's, Cofilin-1 can form cofilin-actin rods that impair axonal transport and synaptic function (PubMed: 24501114). While direct small-molecule inhibitors of Cofilin-1 are largely in the experimental stage, the pathway is frequently targeted via LIMK inhibitors to modulate the phosphorylation state and subsequent actin dynamics.

Other names

CFL1n-cofilin18 kDa phosphoproteinp18Actin-depolymerizing factor

Modulation of actin filament dynamics by inhibiting or promoting the severing and depolymerization of F-actin; often achieved by targeting upstream kinases such as LIMK to alter the phosphorylation state of the Serine-3 residue (PubMed: 15659503, 20473360).