دورية أكاديمية
Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death.
العنوان: | Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death. |
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المؤلفون: | RELIC, Biserka, CHARLIER, Anne, DEROYER, Céline, MALAISE, Olivier, Crine, Yannick, NEUVILLE, Sophie, GILLET, Philippe, DE SENY, Dominique, Malaise, Michel |
المصدر: | Oncotarget, 9 (88), 35830-35843 (2018) |
بيانات النشر: | Impact Journals, 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | RAD23B, autophagy, p62/SQSTM1 phosphorylation, proteasome, serum starvation, Human health sciences, Rheumatology, Sciences de la santé humaine, Rhumatologie |
الوصف: | Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085-induced human synovial fibroblast cell death includes autophagy and p62 downregulation. In this work, we have studied expression of P-Ser349 p62 in human synovial fibroblasts. Results showed that P-Ser349 p62 was not detected in synovial cell extracts unless cells were cultured in the presence of proteasome inhibitor (MG132). MG132 revealed P-Ser349 p62 turnover, that was further increased by concomitant autophagy inhibition and markedly enhanced in serum starved cells. Starvation sensitized synovial fibroblasts to BAY 11-7085 while MG132 protected both non-starved and starved cells from BAY 11-7085-induced cell death. Lentivirus mediated overexpression of phosphorylation-mimetic p62 mutant S349E markedly protected synovial fibroblasts from BAY 11-7085. Inhibitor of Keap1-P-S349 p62 interaction, K67, had synergistic effect with MG132. Starvation increased p62 molecular weight, that was reversed by serum and bovine serum albumin re-feeding. Furthermore, starvation markedly induced RAD23B. Increased endo-beta-N-acetylglucosaminidase (ENGase) turnover was detected in starved synovial fibroblasts. PNGase F treatment produced faster migration p62 form in human synovial tissue extracts but starvation-like p62 form of higher molecular weight in synovial cell extracts. Co-transfection of NGLY1, with p62 or p62 mutants S349A and S349E markedly stabilized p62 expressions in HEK293 cells. Tunicamycin upregulated p62 and protected synovial fibroblasts from BAY 11-7085-induced cell death. These results showed that P-Ser349 p62 has pro-survival role in human synovial fibroblasts and that de-glycosylation events are involved in p62 turnover. |
نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
اللغة: | English |
Relation: | urn:issn:1949-2553 |
DOI: | 10.18632/oncotarget.26295 |
URL الوصول: | https://orbi.uliege.be/handle/2268/234882 |
حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
رقم الأكسشن: | edsorb.234882 |
قاعدة البيانات: | ORBi |
DOI: | 10.18632/oncotarget.26295 |
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