The ubiquitin-proteasome system is a vital proteolytic pathway required for cell homeostasis. However, the turnover mechanism of the proteasome subunit itself is still not understood. Here, we show that the 20S proteasome subunit PSMA7 is subjected to ubiquitination and proteasomal degradation, which was suppressed by PSMA7 phosphorylation at Y106 mediated by the nonreceptor tyrosine kinases c-Abl/Arg. BRCA1 specifically functions as an E3 ubiquitin ligase of PSMA7 ubiquitination. c-Abl/Arg regulates cellular proteasome abundance by controlling the PSMA7 subunit supply. Downregulated PSMA7 level results in decreased proteasome abundance in c-Abl/Arg RNAi-knockdown or c-abl/arg-deficient cells, which demonstrated an increased sensitivity to proteasome inhibition. In response to oxidative stress, the c-Abl-mediated upregulation of proteasome level compensates for the proteasomal activity impairment induced by reactive oxygen species. Abl-kinases-regulated biogenesis and homeostasis of proteasome complexes may be important for understanding related diseases and pathological states.

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phosphorylation mechanism biogenesis proteasome complexes e3 ubiquitin ligase 20s proteasome subunit psma7 reactive oxygen stress cablargdeficient cablarg rnaiknockdown cell homeostasis proteasome abundance tyrosine proteasomal activity

,.c-Abl Regulates Proteasome Abundance by Controlling the Ubiquitin-Proteasomal Degradation of PSMA7 Subunit. 10 (4),.

,"c-Abl Regulates Proteasome Abundance by Controlling the Ubiquitin-Proteasomal Degradation of PSMA7 Subunit" 10

,"c-Abl Regulates Proteasome Abundance by Controlling the Ubiquitin-Proteasomal Degradation of PSMA7 Subunit"