Amot130 Adapts Atrophin-1 Interacting Protein 4 to Inhibit Yes-associated Protein Signaling and Cell Growth
| Autor: | Hyun-Suk Lim, Jacob J. Adler, Ross Cocklin, Misook Oh, Mark G. Goebl, William P. Ranahan, Brigitte L. Heller, Lauren R. Bringman, Clark D. Wells, Robert J. Ingham |
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| Rok vydání: | 2013 |
| Předmět: |
Transcription
Genetic Ubiquitin-Protein Ligases Protein Serine-Threonine Kinases Biochemistry WW domain Ubiquitin Humans education Molecular Biology Adaptor Proteins Signal Transducing Cell Proliferation Hippo signaling pathway education.field_of_study biology Protein Stability Cell growth Microfilament Proteins Membrane Proteins Signal transducing adaptor protein YAP-Signaling Proteins Cell Biology Phosphoproteins Ubiquitin ligase Cell biology Repressor Proteins HEK293 Cells Angiomotins Gene Expression Regulation Proteolysis biology.protein Intercellular Signaling Peptides and Proteins Atrophin-1 Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 288:15181-15193 |
| ISSN: | 0021-9258 |
| Popis: | The adaptor protein Amot130 scaffolds components of the Hippo pathway to promote the inhibition of cell growth. This study describes how Amot130 through binding and activating the ubiquitin ligase AIP4/Itch achieves these effects. AIP4 is found to bind and ubiquitinate Amot130 at residue Lys-481. This both stabilizes Amot130 and promotes its residence at the plasma membrane. Furthermore, Amot130 is shown to scaffold a complex containing overexpressed AIP4 and the transcriptional co-activator Yes-associated protein (YAP). Consequently, Amot130 promotes the ubiquitination of YAP by AIP4 and prevents AIP4 from binding to large tumor suppressor 1. Amot130 is found to reduce YAP stability. Importantly, Amot130 inhibition of YAP dependent transcription is reversed by AIP4 silencing, whereas Amot130 and AIP4 expression interdependently suppress cell growth. Thus, Amot130 repurposes AIP4 from its previously described role in degrading large tumor suppressor 1 to the inhibition of YAP and cell growth. |
| Databáze: | OpenAIRE |
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