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An alternative pathway for gene regulation by Myc
Author(s) -
Peukert Karen,
Staller Peter,
Schneider Andreas,
Carmichael Gordon,
Hänel Frank,
Eilers Martin
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.18.5672
Subject(s) - biology , transactivation , basic helix loop helix , transcription factor , promoter , microbiology and biotechnology , transcription (linguistics) , gene expression , gene , dna binding protein , genetics , linguistics , philosophy
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; M yc‐ i nteracting Z n 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 .