Proteasome 26S subunit, non-ATPase 10 (PSMD10)

Gankyrin (PSMD10) is a 25 kDa oncoprotein comprising seven ankyrin repeats. It acts as a non-ATPase regulatory subunit of the 19S activator of the 26S proteasome, mediating protein-protein interactions involved in cell cycle control, protein degradation, and oncogenic signaling[1][2][3][5]. Gankyrin binds and negatively regulates key tumor suppressors—including retinoblastoma protein (Rb) and p53—by accelerating their ubiquitylation and proteasomal degradation via interactions with CDK4 and MDM2, respectively[1][5][7]. Overexpression and dysregulation of gankyrin are strongly associated with several human cancers, particularly hepatocellular carcinoma, where it promotes tumorigenesis, proliferation, and metastasis[3][4][5][7]. Its structure features a repeated ankyrin motif facilitating protein interactions, and its disruption is being explored as a strategy for anti-tumor therapy[1][2][8].

Other names

Gankyrinp28GANKP28PSMD10Gann ankyrin repeat protein

Inhibition of gankyrin would impair its ability to bind CDK4, Mdm2, Rb, and proteasome components, thereby restoring tumor suppressor functions (e.g., p53, Rb), slowing cell cycle progression, and promoting apoptosis in cancer cells[3][4][5][7][8].