title: TSA-induced JMJD2B downregulation is associated with cyclin B1-dependent survivin degradation and apoptosis in LNCap cells.
abstract: Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to induce apoptosis of cancer cells, and a significant number of genes have been identified as potential effectors responsible for HDAC inhibitor-induced apoptosis. However, the mechanistic actions of these HDAC inhibitors in this process remain largely undefined. We here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor trichostatin A (TSA) resulted in downregulation of the Jumonji domain-containing protein 2B (JMJD2B). We also found that the TSA-mediated decrease in survivin expression in LNCap cells was partly attributable to downregulation of JMJD2B expression. This effect was attributable to the promoted degradation of survivin protein through inhibition of Cyclin B1/Cdc2 complex-mediated survivin Thr34 phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA-induced apoptosis by regulating the Cyclin B1-dependent survivin degradation to potentiate the apoptosis pathways.
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Pingfu
authors.initials: P
authors.lastname: Hou
authors.forename: Chenyan
authors.initials: C
authors.lastname: Shangguan
authors.forename: Ruosi
authors.initials: R
authors.lastname: Yao
authors.forename: Weina
authors.initials: W
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiang
authors.initials: J
authors.lastname: Tan
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; C534699:CCNB1 protein, human; D056744:Cyclin B1; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; C012589:trichostatin A; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human