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Updated: Sep 26, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Yaf2 inhibits Myc biological function
Britta Mädge1, Christoph Geisen, Tarik Möröy
1Division of Cytogenetics-H0400, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Abstract:
The proto-oncogenes of the myelocytomatosis viral oncogene homolog (MYC) family, including MYC, MYCN and MYCL, encode nuclear proteins that act as transcription factors. The Myc protein is the best studied member of this family and is involved in cell cycle regulation, differentiation and cell death. We have previously demonstrated that the zinc-finger protein Yaf2 interacts with the central region of MycN and enhances MycN dependent transcriptional activation. Here we show that Yaf2 also binds to the Myc protein in vivo and in vitro. In contrast to the activating effect on MycN function, Yaf2 inhibits Myc mediated transactivation and transformation. This differential influence on two members of the Myc family gives insight into a new mechanism to modulate the biological activities of Myc transcription factors.
Insights
The zinc-finger protein Yaf2 interacts with MYC family proteins. Yaf2 enhances MYCN activity but inhibits MYC, revealing a novel regulatory mechanism for these key transcription factors.
Area of Science:
- Molecular Biology
- Oncogenes
- Transcription Factors
Background:
- The MYC family (MYC, MYCN, MYCL) encodes nuclear transcription factors crucial for cell cycle, differentiation, and apoptosis.
- The zinc-finger protein Yaf2 was previously shown to enhance MYCN-dependent transcription.
Purpose of the Study:
- To investigate the interaction between Yaf2 and the MYC protein.
- To elucidate the functional consequences of Yaf2 binding to MYC and MYCN.
Main Methods:
- In vivo and in vitro binding assays to confirm Yaf2-Myc interaction.
- Functional assays to assess the impact of Yaf2 on MYC and MYCN transcriptional activity and transformation potential.
Main Results:
- Yaf2 binds to the MYC protein both in vivo and in vitro.
- Unlike its activating effect on MYCN, Yaf2 inhibits MYC-mediated transactivation and transformation.
- Demonstrates differential regulation of MYC family members by Yaf2.
Conclusions:
- Yaf2 exhibits distinct regulatory effects on MYC and MYCN.
- This differential modulation by Yaf2 offers a novel mechanism for controlling MYC transcription factor activity in biological processes.
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