Proteasome-mediated proteolysis is a primary protein degradation pathway in cells. The present study demonstrates that c-AbI and Arg (abi-related gene)tyrosine kinases associate with and phosphorylate the proteasome PSMA7 (alpha 4) subunit at Tyr-153. Consequently, proteasome-dependent proteolysis is compromised. Notably, cells expressing a phosphorylation mutant of PSMA7(Y153F) display impaired G1/S transition and S/G2 progression, highlighting the biological significance of tyrosine phosphorylation of a proteasome subunit as an important cellular regulatory control.