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PDBsum entry 2m1r
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Gene regulation
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PDB id
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2m1r
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References listed in PDB file
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Key reference
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Title
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Functional impact of cancer-Associated mutations in the tumor suppressor protein ing4.
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Authors
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A.Moreno,
A.Palacios,
J.L.Orgaz,
B.Jimenez,
F.J.Blanco,
I.Palmero.
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Ref.
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Carcinogenesis, 2010,
31,
1932-1938.
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PubMed id
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Abstract
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Inhibitor of growth 4 (ING4) is a member of the ING family of tumor suppressor
proteins. In this study, we have analyzed the impact of two mutations in ING4
associated with human tumors (Y121N and N214D), testing their behavior in a
series of functional, biochemical and structural analyses. We report that the
N214D mutation dramatically dampened the ability of ING4 to inhibit
proliferation, anchorage-independent growth or cell migration or to sensitize to
cell death. In turn, the Y121N mutant did not differ significantly from
wild-type ING4 in our assays. Neither of the mutations altered the normal
subcellular localization of ING4, showing predominantly nuclear accumulation. We
investigated the molecular basis of the defect in the activity of the N214D
mutant. The folding and ability to bind histone marks of ING4 was not
significantly altered by this mutation. Instead, we found that the functional
impairment of the N214D mutant correlates with reduced protein stability due to
increased proteasome-mediated degradation. In summary, our data demonstrates
that a point mutation of ING4 associated to human tumors leads to the loss of
several essential functions of ING4 pertinent to tumor protection and highlight
the importance of ING4 function to prevent tumorigenesis.
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