title: Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells.
abstract: Autophagy can protect cells while also contributing to cell damage, but the precise interplay between apoptosis and autophagy and the contribution of autophagy to cell death are still not clear. Previous studies have shown that supranutritional doses of sodium selenite promote apoptosis in human leukemia NB4 cells. Here, we report that selenite treatment triggers opposite patterns of autophagy in the NB4, HL60, and Jurkat leukemia cell lines during apoptosis and provide evidence that the suppressive effect of selenite on autophagy in NB4 cells is due to the decreased expression of the chaperone protein Hsp90 (heat shock protein 90), suggesting a novel regulatory function of Hsp90 in apoptosis and autophagy. Excessive or insufficient expression indicates that Hsp90 protects NB4 cells from selenite-induced apoptosis, and selenite-induced decreases in the expression of Hsp90, especially in NB4 cells, inhibit the activities of the IκB kinase/nuclear factor-κB (IKK/NF-κB) signaling pathway, leading to less nuclear translocation and inactivation of NF-κB and the subsequent weak binding of the becn1 promoter, which facilitates the transition from autophagy to apoptosis. Taken together, our observations provide novel insights into the mechanisms underlying the balance between apoptosis and autophagy, and we also identified Hsp90-NF-κB-Beclin1 as a potential biological pathway for signaling the switch from autophagy to apoptosis in selenite-treated NB4 cells.
authors.affiliation: Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Wang
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Li
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.forename: Zhushi
authors.initials: Z
authors.lastname: Li
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D020868:Gene Silencing; D018922:HL-60 Cells; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019169:Jurkat Cells; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018038:Sodium Selenite / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D018841:HSP90 Heat-Shock Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051550:I-kappa B Kinase; D018038:Sodium Selenite