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Amot130 Adapts Atrophin-1 Interacting Protein 4 to Inhibit Yes-associated Protein Signaling and Cell Growth
- Source :
- Journal of Biological Chemistry. 288:15181-15193
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....51a8dc5d3dc5ec9d0e50ff916e75d322