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 - Beierg, Rudi
AU - Bernard, Sandra
AU - Quarto, Micaela
AU - Capra, Maria
AU - Goettig, Stephan
AU - Kogel, Ulrike
AU - Scheffnerg, Martin
AU - Helin, Kristian
AU - Eilers, Martin
N1 - Funding Information:
We thank D. Piccini for the help in generating monoclonal antibodies to HectH9, Bill Tansey (Cold Spring Harbor Laboratories) for the gift of Myc expression plasmids, Norbert Kraut (Boehringer Ingelheim, Vienna) for access to gene expression databases, and Birgit Samans (IMT) for microarray analysis. F.M. was supported by a fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC). This study was supported by the Deutsche Forschungsgemeinschaft (M.E. and M.S.), the FP5 program of the European Union (K.H. and M.E.), the Carreras-Foundation (S.A.), the Fritz Thyssen Stiftung (M.E.), the Associazione Italiana per la Ricerca sul Cancro (K.H.), and the Danish Ministry for Science, Technology, and Innovation (K.H.).
PY - 2005/11/4
Y1 - 2005/11/4
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.
UR - http://www.scopus.com/inward/record.url?scp=27544473311&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2005.08.016
DO - 10.1016/j.cell.2005.08.016
M3 - Article
SN - 0092-8674
VL - 123
SP - 409
EP - 421
JO - Cell
JF - Cell
IS - 3
ER -