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PDBsum entry 2m6y
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References listed in PDB file
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Key reference
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Title
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Structure and function of human dnaj homologue subfamily a member 1 (dnaja1) and its relationship to pancreatic cancer.
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Authors
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J.L.Stark,
K.Mehla,
N.Chaika,
T.B.Acton,
R.Xiao,
P.K.Singh,
G.T.Montelione,
R.Powers.
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Ref.
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Biochemistry, 2014,
53,
1360-1372.
[DOI no: ]
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PubMed id
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Abstract
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Pancreatic cancer has a dismal 5 year survival rate of 5.5% that has not been
improved over the past 25 years despite an enormous amount of effort. Thus,
there is an urgent need to identify truly novel yet druggable protein targets
for drug discovery. The human protein DnaJ homologue subfamily A member 1
(DNAJA1) was previously shown to be downregulated 5-fold in pancreatic cancer
cells and has been targeted as a biomarker for pancreatic cancer, but little is
known about the specific biological function for DNAJA1 or the other members of
the DnaJ family encoded in the human genome. Our results suggest the
overexpression of DNAJA1 suppresses the stress response capabilities of the
oncogenic transcription factor, c-Jun, and results in the diminution of cell
survival. DNAJA1 likely activates a DnaK protein by forming a complex that
suppresses the JNK pathway, the hyperphosphorylation of c-Jun, and the
anti-apoptosis state found in pancreatic cancer cells. A high-quality nuclear
magnetic resonance solution structure of the J-domain of DNAJA1 combined with a
bioinformatics analysis and a ligand affinity screen identifies a potential DnaK
binding site, which is also predicted to overlap with an inhibitory binding
site, suggesting DNAJA1 activity is highly regulated.
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