Abstract
In this study, we discovered that NSD2 specifically interacts with the DNA-binding domain of androgen receptor (AR) via its HMG domain, and the nuclear translocation of both NSD2 and AR is enhanced in the presence of ligand. Furthermore, we also demonstrated that the over expression of NSD2, but not of NSD2 (DeltaSET) HMT-activity defective mutant, enhanced the mRNA level of PSA in a dose-dependent manner. A chromatin immunoprecipitation assay showed that NSD2 protein is recruited to the enhancer region of the PSA gene by AR in an agonist-enhanced manner. Taken together, these results uncover a potential role for NSD2 in AR-mediated transcription, implicating NSD2 in prostate carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Base Sequence
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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DNA Primers / genetics
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Enhancer Elements, Genetic
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Histone-Lysine N-Methyltransferase / chemistry
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism*
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Histones / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Ligands
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Male
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Prostate-Specific Antigen / genetics
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Prostate-Specific Antigen / metabolism
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Prostatic Neoplasms / etiology
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Protein Interaction Domains and Motifs
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Receptors, Androgen / chemistry
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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AR protein, human
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DNA Primers
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Histones
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Homeodomain Proteins
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Ligands
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NKX3-1 protein, human
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Receptors, Androgen
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Recombinant Proteins
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Repressor Proteins
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Transcription Factors
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Histone-Lysine N-Methyltransferase
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NSD2 protein, human
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Prostate-Specific Antigen