Tumor cell‐specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase

• Published in: EMBO molecular medicine Vol. 6; no. 12; pp. 1525 - 1541
• Main Authors: Peter, Stefanie, Bultinck, Jennyfer, Myant, Kevin, Jaenicke, Laura A, Walz, Susanne, Müller, Judith, Gmachl, Michael, Treu, Matthias, Boehmelt, Guido, Ade, Carsten P, Schmitz, Werner, Wiegering, Armin, Otto, Christoph, Popov, Nikita, Sansom, Owen, Kraut, Norbert, Eilers, Martin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; John Wiley & Sons, Inc; EMBO Press; BlackWell Publishing Ltd; Springer Nature
• Subjects: Animals; Cancer; Carcinogenesis; Cell culture; Cell Line, Tumor; Cell Proliferation; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - physiopathology; EMBO03; EMBO12; EMBO28; Epithelial cells; Experiments; Gene expression; Gene Expression Regulation, Neoplastic; Gene silencing; Genetic transcription; Humans; HUWE1; Huwe1 protein; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Laboratories; Ligases; Mice; Mice, SCID; MIZ1; MYC; Myc protein; Oncogene Protein p55(v-myc) - antagonists & inhibitors; Oncogene Protein p55(v-myc) - genetics; Oncogene Protein p55(v-myc) - metabolism; Protein Binding; Proteins; Research Article; Signal transduction; Small Molecule Libraries - administration & dosage; Small Molecule Libraries - pharmacology; Stem cells; Transcription activation; Transcriptional Activation; Tumor cells; Tumor Suppressor Proteins; Tumorigenesis; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; ubiquitination; Xenografts; HUWE1; colorectal cancer; ubiquitination; MYC; MIZ1

Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF‐BP1, MULE) associates with both MYC and the MYC‐associated protein MIZ1. We show here that HUWE1 is required for growth of colorecta...