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Prep1, a novel functional partner of Pbx proteins
J Berthelsen1, V Zappavigna, F Mavilio
1Dipartimento di Genetica e Biologia dei Microrganismi dell'Università, DIBIT, H.S. Raffaele, via Olgettina 58, 20132, Milan, Italy.
The EMBO Journal
|April 18, 1998
Summary
Researchers identified Prep1, a novel human homeodomain protein, as a key subunit of the UEF3 transcription factor. Prep1 forms a stable complex with Pbx proteins, enhancing DNA binding to regulate gene expression.
Area of Science:
- Molecular Biology
- Gene Regulation
- Protein Interactions
Background:
- The UEF3 transcription factor regulates the urokinase plasminogen activator (uPA) gene enhancer.
- UEF3 is a multi-subunit complex crucial for gene regulation.
- The UEF3 DNA target site is a regulatory element in growth factor and protease gene promoters.
Purpose of the Study:
- To clone and characterize subunits of the UEF3 complex.
- To identify the novel human homeodomain protein within the UEF3 complex.
- To elucidate the interaction between UEF3 subunits and their role in DNA binding.
Main Methods:
- Cloning of cDNA encoding a novel human homeodomain protein, named Prep1.
- Characterization of Prep1's homeodomain and its relation to other known homeodomains.
- Identification of the other UEF3 subunit as a Pbx protein family member and analysis of Prep1-Pbx interactions.
Main Results:
- Cloning of cDNA encoding Prep1, a novel human homeodomain protein.
- Prep1 belongs to the TALE class of homeodomains, related to TGIF and Meis1, recognizing a TGACAG motif.
- Prep1 forms a stable complex with Pbx proteins independently of DNA binding, leading to enhanced DNA binding affinity for the uPA promoter target site.
Conclusions:
- Prep1 is a novel human homeodomain protein and a subunit of the UEF3 transcription factor.
- Prep1 forms a stable heterodimer with Pbx proteins.
- The Prep1-Pbx complex exhibits strong DNA binding affinity, indicating Prep1 is a stable intracellular partner of Pbx in vivo.