The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation |
| |
Authors: | Adhikary Sovana Marinoni Federica Hock Andreas Hulleman Esther Popov Nikita Beier Rudi Bernard Sandra Quarto Micaela Capra Maria Goettig Stephan Kogel Ulrike Scheffner Martin Helin Kristian Eilers Martin |
| |
Affiliation: | Institute for Molecular Biology and Tumor Research, University of Marburg, Emil-Mannkopff-Str.2, 35033 Marburg, Germany. |
| |
Abstract: | The Myc oncoprotein forms a binary activating complex with its partner protein, Max, and a ternary repressive complex that, in addition to Max, contains the zinc finger protein Miz1. Here we show that the E3 ubiquitin ligase HectH9 ubiquitinates Myc in vivo and in vitro, forming a lysine 63-linked polyubiquitin chain. Miz1 inhibits this ubiquitination. HectH9-mediated ubiquitination of Myc is required for transactivation of multiple target genes, recruitment of the coactivator p300, and induction of cell proliferation by Myc. HectH9 is overexpressed in multiple human tumors and is essential for proliferation of a subset of tumor cells. Our results suggest that site-specific ubiquitination regulates the switch between an activating and a repressive state of the Myc protein, and they suggest a strategy to interfere with Myc function in vivo. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|