Amot130 Adapts Atrophin-1 Interacting Protein 4 to Inhibit Yes-associated Protein Signaling and Cell Growth

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

doi:10.1074/jbc.m112.446534

Cited by 54 publications

(74 citation statements)

References 53 publications

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“…Strikingly, Amot130 (S175A) highly concentrated at thickened F-actin stress fibers (Fig. S3F), similar to the localization of the Amot130 (K481R) mutant, which has reduced ubiquitination by AIP4 (25). Thus, the nonphosphorylated forms of Amot130 and AmotL1 likely bind and rearrange actin (30,31).…”

Section: Significancementioning

confidence: 70%

“…The Nedd4 ubiquitin ligase AIP4 binds and ubiquitinates Amot130, resulting in a reduction in Amot130 residence at actin fibers and a significant enhancement of the stability of Amot130 protein (25). Thus, the role of serum and LATS1 in promoting the Amot130-AIP4 complex was examined.…”

Section: Significancementioning

confidence: 99%

“…This analysis was carried out in MCF7 cells due to their high AIP4 levels (25), which sensitize them to effects of phosphorylation of Amot130. Expression of wild-type Amot130 reduced the half-life of YAP to 8.9 h, following incubation with cycloheximide, as previously shown (25). However, cells expressing Amot130 (S175A) showed no detectable reduction of YAP stability over this period (Fig.…”

Section: The Amot130-aip4 Complex Promotes the Ubiquitination Of Yap Inmentioning

confidence: 99%

“…Because ubiquitination of Amot130 reduces its association with actin stress fibers and increases its stability (25), wild-type Amot130 and Amot130 (S175A) were compared for similar behaviors. YFP-tagged wild-type Amot130, similar to previous reports, localized mainly at intercellular contacts (21), likely through membrane association (Fig.…”

Section: Significancementioning

confidence: 99%

“…Amot associates with cell junctions and binds apical polarity proteins, which underlie its ability to control cell shape and migration (20)(21)(22)(23). The 130 kDa isoform of Amot (Amot130), unlike the 80-kDa isoform (Amot80) that promotes cell growth (24), binds and inhibits YAP through cytosolic sequestration (17,18) and by facilitating its degradation (25) in a manner that can be independent of YAP phosphorylation by LATS1/2 at residue Ser-127 (17,18).…”

mentioning

confidence: 99%

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Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Adler¹,

Johnson²,

Heller³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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132

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Significance This study defines a unique mechanism controlling the activation of Hippo signaling and consequent inhibition of cell growth. Specifically, serum starvation is found to induce the large tumor suppressor (LATS)1/2 kinases to phosphorylate and thus stabilize the 130 kDa isoform of the membrane-associated polarity protein angiomotin (Amot130). As a consequence, Amot130 recruits the E3 protein-ubiquitin ligase atrophin-1 interacting protein 4. This multiprotein complex then signals the degradation of Yes-associated protein (YAP) and the inhibition of cell growth. These findings significantly modify our current view that YAP phosphorylation by LATS1/2 is sufficient for its inhibition in mammals and thus for growth arrest.

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Section: Significancementioning

confidence: 70%

Section: Significancementioning

confidence: 99%

Section: The Amot130-aip4 Complex Promotes the Ubiquitination Of Yap Inmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Adler¹,

Johnson²,

Heller³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

130

132

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YAPping about and not forgetting TAZ

et al. 2019

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The Hippo pathway has emerged as a major eukaryotic signalling pathway and is increasingly the subject of intense interest, as are the key effectors of canonical Hippo signalling, YES‐associated protein (YAP) and TAZ. The Hippo pathway has key roles in diverse biological processes, including network signalling regulation, development, organ growth, tissue repair and regeneration, cancer, stem cell regulation and mechanotransduction. YAP and TAZ are multidomain proteins and function as transcriptional coactivators of key genes to evoke their biological effects. YAP and TAZ interact with numerous partners and their activities are controlled by a complex set of processes. This review provides an overview of Hippo signalling and its role in growth. In particular, the functional domains of YAP and TAZ and the complex mechanisms that regulate their protein stability and activity are discussed. Notably, the similarities and key differences are highlighted between the two paralogues including which partner proteins interact with which functional domains to regulate their activity.

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Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer

Zhao,

Li,

Cheng

et al. 2024

Advanced Science

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Myofibrillogenesis regulator‐1 (MR‐1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR‐1 on the development and metastasis of non‐small cell lung cancer (NSCLC). MR‐1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR‐1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3‐ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR‐1 on NICD3 is achieved through the mono‐ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR‐1 and NICD3. Elevated MR‐1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR‐1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR‐1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.

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Amot130 Adapts Atrophin-1 Interacting Protein 4 to Inhibit Yes-associated Protein Signaling and Cell Growth

Cited by 54 publications

References 53 publications

Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

YAPping about and not forgetting TAZ

Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer

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