title: c-Abl regulates proteasome abundance by controlling the ubiquitin-proteasomal degradation of PSMA7 subunit.
abstract: 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.
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Dapei
authors.initials: D
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Qincai
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Institute of Health Sciences, Anhui University, Hefei 230601, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Tao
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Beijing Institute of Disease Control and Prevention, Beijing 100071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Rao
authors.initials: R
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Health Sciences, Anhui University, Hefei 230601, China.
authors.forename: David T
authors.initials: DT
authors.lastname: Weaver
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China. Electronic address: liux931932@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China. Electronic address: caoc@nic.bmi.ac.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002850:Chromatography, Gel; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
chemical_list: D025801:Ubiquitin; D016315:Proto-Oncogene Proteins c-abl; C488662:PSMA7 protein, human; D046988:Proteasome Endopeptidase Complex