Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating enhancer binding protein 2alpha complex formation.

HLJ1, a member of the heat shock protein 40 chaperone family, is a newly identified tumor suppressor that has been implicated in tumorigenesis and metastasis in non-small cell lung cancer. However, the mechanism of HLJ1 action is presently obscure. In this study, we report that HLJ1 specifically interacts with the ...
nuclear protein nucleophosmin (NPM1), forming a multiprotein complex that alters the nucleolar distribution and oligomerization state of NPM1. Enforced accumulation of NPM1 oligomers by overexpression in weakly invasive but high HLJ1-expressing cells induced the activity of signal transducer and activator of transcription 3 (STAT3) and increased cellular migration, invasiveness, and colony formation. Furthermore, silencing HLJ1 accelerated NPM1 oligomerization, inhibited the activity of transcription corepressor activating enhancer binding protein 2alpha (AP-2alpha), and increased the activities of matrix metalloproteinase-2 (MMP-2) and STAT3. Our findings suggest that HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2alpha to the MMP-2 promoter.
Mesh Terms:
Adenocarcinoma, Cell Nucleus, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, HSP40 Heat-Shock Proteins, Humans, Lung Neoplasms, Matrix Metalloproteinase 2, Multiprotein Complexes, Neoplasm Invasiveness, Nuclear Proteins, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Protein Transport, Transcription Factor AP-2, Transfection, Tumor Cells, Cultured, Tumor Suppressor Proteins
Cancer Res.
Date: Feb. 15, 2010
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