LZTR1 is a regulator of RAS ubiquitination and signaling

• Published in: Science (American Association for the Advancement of Science) Vol. 362; no. 6419; pp. 1171 - 1177
• Main Authors: Bigenzahn, Johannes W., Collu, Giovanna M., Kartnig, Felix, Pieraks, Melanie, Vladimer, Gregory I., Heinz, Leonhard X., Sedlyarov, Vitaly, Schischlik, Fiorella, Fauster, Astrid, Rebsamen, Manuele, Parapatics, Katja, Blomen, Vincent A., Müller, André C., Winter, Georg E., Kralovics, Robert, Brummelkamp, Thijn R., Mlodzik, Marek, Superti-Furga, Giulio
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 07.12.2018
• Subjects: Adapter proteins; Adapters; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; BCR-ABL protein; Cell Line, Tumor; Chronic myeloid leukemia; Cullin; Deactivation; Developmental disabilities; Drosophila melanogaster; Drug resistance; Drug Resistance, Neoplasm - genetics; Fruit flies; Fusion protein; Fusion Proteins, bcr-abl - antagonists & inhibitors; Gain of Function Mutation; Gene Knockdown Techniques; Genetic screening; Guanosine; Homology; Humans; Imidazoles - pharmacology; Imidazoles - therapeutic use; Inactivation; Inhibitors; Isoforms; Kinases; Leucine; Leucine zipper proteins; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - epidemiology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Localization; Loss of Function Mutation; MAP kinase; MAP Kinase Signaling System - genetics; Mutation; Myeloid leukemia; Noonan's syndrome; Phenotypes; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Proteins; Proto-Oncogene Proteins p21(ras) - metabolism; Pyridazines - pharmacology; Pyridazines - therapeutic use; Sarcoma; Signal Transduction; Signaling; Transcription; Transcription Factors - genetics; Transcription Factors - physiology; Triphosphatase; Tyrosine; Ubiquitination; Ubiquitination - genetics

The protein LZTR1 is mutated in human cancers and developmental diseases. Work from two groups now converges to implicate the protein in regulating signaling by the small guanosine triphosphatase RAS. Steklov et al. showed that mice haploinsufficient for LZTR1 recapitulated aspects of the human dise...