title: Genotoxic stress/p53-induced DNAJB9 inhibits the pro-apoptotic function of p53.
abstract: DNAJB9 is a recently isolated member of the molecular chaperone gene family, whose precise function is largely unknown. In the present study, we have identified DNAJB9 as an inducible gene of the tumor suppressor p53. DNAJB9 expression was induced by p53 or genotoxic stress in a p53-dependent manner, which was mediated by the Ras/Raf/ERK pathway. In addition, depletion of DNAJB9 by using siRNAs greatly increased genotoxic stress/p53-induced apoptosis, suggesting that DNAJB9 inhibits the pro-apoptotic function of p53. We also found that DNAJB9 physically interacts with p53 through its J domain, through which it inhibits the pro-apoptotic function of p53. Moreover, DNAJB9 colocalized with p53 in both cytoplasm and nucleus under genotoxic conditions. Together, these results demonstrate that DNAJB9 is a downstream target of p53 that belongs to the group of negative feedback regulators of p53.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Institute for Systems Biology, Seattle, WA, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, South Korea.
authors.forename: J I
authors.initials: JI
authors.lastname: Heo
authors.affiliation: Department of Biochemistry, College of Medicine, Dankook University, Cheonan, South Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kwak
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: J A
authors.initials: JA
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C478021:DNAJB9 protein, human; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53