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EMBO J. 1997 Sep 15;16(18):5672-86.

An alternative pathway for gene regulation by Myc.

Author information

  • 1Hans-Knöll-Institut für Naturstoff-Forschung, Department of Cell and Molecular Biology, Beutenbergstrasse 11, 07745 Jena, Germany.

Abstract

The c-Myc protein activates transcription as part of a heteromeric complex with Max. However, Myc-transformed cells are characterized by loss of expression of several genes, suggesting that Myc may also repress gene expression. Two-hybrid cloning identifies a novel POZ domain Zn finger protein (Miz-1; Myc-interacting Zn finger protein-1) that specifically interacts with Myc, but not with Max or USF. Miz-1 binds to start sites of the adenovirus major late and cyclin D1 promoters and activates transcription from both promoters. Miz-1 has a potent growth arrest function. Binding of Myc to Miz-1 requires the helix-loop-helix domain of Myc and a short amphipathic helix located in the carboxy-terminus of Miz-1. Expression of Myc inhibits transactivation, overcomes Miz-1-induced growth arrest and renders Miz-1 insoluble in vivo. These processes depend on Myc and Miz-1 association and on the integrity of the POZ domain of Miz-1, suggesting that Myc binding activates a latent inhibitory function of this domain. Fusion of a nuclear localization signal induces efficient nuclear transport of Miz-1 and impairs the ability of Myc to overcome transcriptional activation and growth arrest by Miz-1. Our data suggest a model for how gene repression by Myc may occur in vivo.

PMID:
9312026
[PubMed - indexed for MEDLINE]
PMCID:
PMC1170199
Free PMC Article
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