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

TY - JOUR

T1 - The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation.

AU - Adhikary, Sovana

AU - Marinoni, Federica

AU - Hock, Andreas

AU - Hulleman, Esther

AU - Popov, Nikita

AU - Beier, Rudi

AU - Bernard, Sandra

AU - Quarto, Micaela

AU - Capra, Maria

AU - Goettig, Stephan

AU - Kogel, Ulrike

AU - Scheffner, Martin

AU - Helin, Kristian

AU - Eilers, Martin

N1 - Keywords: Amino Acid Sequence; Animals; Cell Line, Tumor; Cell Proliferation; DNA-Binding Proteins; Genes, myc; Humans; Kruppel-Like Transcription Factors; Mice; Molecular Sequence Data; Neoplasms; Polyubiquitin; Proto-Oncogene Proteins c-myc; Trans-Activation (Genetics); Transcription Factors; Ubiquitin-Protein Ligases; p300-CBP Transcription Factors

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2005.08.016

DO - 10.1016/j.cell.2005.08.016

M3 - Journal article

C2 - 16269333

SN - 0092-8674

VL - 123

SP - 409

EP - 421

JO - Cell

JF - Cell

IS - 3

ER -