Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9.

PLU-1 is a large (1544 amino acids) nuclear protein that is highly expressed in breast cancers and is proposed to function as a regulator of gene expression. A yeast two-hybrid screen using PLU-1 as bait has identified two unrelated PLU-1 interacting proteins, namely brain factor-1 (BF-1) and paired box 9 ...
(PAX9), both of which are developmental transcription factors. BF-1 and PAX9 interact with PLU-1 via a novel conserved sequence motif (Ala-X-Ala-Ala-X-Val-Pro-X4-Val-Pro-X8-Pro, termed the VP motif), because deletion or site-directed mutagenesis of this motif in either protein abolishes PLU-1 interaction in vivo. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression. Mutation of the PLU-1 binding motifs in BF-1 and PAX9 abolishes the observed PLU-1 co-repression activity. These data support a role for PLU-1 acting as a transcriptional co-repressor of two unrelated developmental transcription factors. Because both BF-1 and PAX proteins interact with members of the groucho co-repressor family, it is plausible that PLU-1 has a role in groucho-mediated transcriptional repression.
Mesh Terms:
Amino Acid Sequence, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, Conserved Sequence, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Kidney, Molecular Sequence Data, Mutagenesis, Site-Directed, Neoplasm Proteins, Nerve Tissue Proteins, Nuclear Proteins, PAX9 Transcription Factor, Repressor Proteins, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Jun. 06, 2003
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