The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation

Sovana Adhikary, Federica Marinoni, Andreas Hock, Esther Hulleman, Nikita Popov, Rudi Beierg, Sandra Bernard, Micaela Quarto, Maria Capra, Stephan Goettig, Ulrike Kogel, Martin Scheffnerg, Kristian Helin, Martin Eilers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.
Originele taal-2Engels
Pagina's (van-tot)409-421
TijdschriftCell
Volume123
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 4 nov. 2005
Extern gepubliceerdJa

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