Genotoxic stress/p53-induced DNAJB9 inhibits the pro-apoptotic function of p53

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...

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Bibliographic Details
Published in:Cell death and differentiation 2015-01, Vol.22 (1), p.86-95
Main Authors: Lee, H J, Kim, J M, Kim, K H, Heo, J I, Kwak, S J, Han, J A
Format: Article
Language:English
Subjects:
631/45/612/1981
631/67/581
631/80/82/23
631/80/86
Animals
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell cycle
Cell Cycle Analysis
Cell death
Cell Line, Tumor
Cell Nucleus - genetics
Cell Nucleus - metabolism
Cytoplasm - genetics
Cytoplasm - metabolism
DNA Damage
Endoplasmic reticulum
Genes
Genomes
Heat shock proteins
HSP40 Heat-Shock Proteins - genetics
HSP40 Heat-Shock Proteins - metabolism
Humans
Life Sciences
MAP Kinase Signaling System
Medicine
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Knockout
Molecular biology
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Original Paper
Protein Binding
Protein Structure, Tertiary
Stem Cells
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1350-9047
1476-5403
DOI:10.1038/cdd.2014.116