Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth

Jacob J. Adler, Brigitte L. Heller, Lauren R. Bringman, William P. Ranahan, Ross R. Cocklin, Mark Goebl, Misook Oh, Hyun-Suk Lim, Robert J. Ingham, Clark Wells

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15181-15193
Number of pages13
JournalJournal of Biological Chemistry
Volume288
Issue number21
DOIs
StatePublished - May 24 2013

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Cell growth
Growth
Proteins
Tumors
Protein Stability
Ubiquitination
Ligases
Ubiquitin
Transcription
Cell membranes
Scaffolds (biology)
Neoplasms
Scaffolds
Cell Membrane
atrophin-1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth. / Adler, Jacob J.; Heller, Brigitte L.; Bringman, Lauren R.; Ranahan, William P.; Cocklin, Ross R.; Goebl, Mark; Oh, Misook; Lim, Hyun-Suk; Ingham, Robert J.; Wells, Clark.

In: Journal of Biological Chemistry, Vol. 288, No. 21, 24.05.2013, p. 15181-15193.

Research output: Contribution to journalArticle

Adler, Jacob J. ; Heller, Brigitte L. ; Bringman, Lauren R. ; Ranahan, William P. ; Cocklin, Ross R. ; Goebl, Mark ; Oh, Misook ; Lim, Hyun-Suk ; Ingham, Robert J. ; Wells, Clark. / Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 21. pp. 15181-15193.
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AU - Heller, Brigitte L.

AU - Bringman, Lauren R.

AU - Ranahan, William P.

AU - Cocklin, Ross R.

AU - Goebl, Mark

AU - Oh, Misook

AU - Lim, Hyun-Suk

AU - Ingham, Robert J.

AU - Wells, Clark

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