Akt Phosphorylates the Yes-Associated Protein, YAP, to Induce Interaction with 14-3-3 and Attenuation of p73-Mediated Apoptosis

Basu, Soumalee; Totty, Nicholas F.; Irwin, Meredith S.; Sudol, Marius; Downward, Julian

doi:10.1016/s1097-2765(02)00776-1

Cited by 741 publications

(726 citation statements)

References 38 publications

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“…Similarly, Dong et al (2007) suggested that YAP-1 plays a role in size control mechanism in Drosophila and mammals . In contrast, other studies have shown that YAP-1 has antitumoral properties (Basu et al, 2003;Matallanas et al, 2007;Strano and Blandino, 2007). Furthermore, YAP-1 mRNA upregulation correlates with improved survival in breast cancer patients (Matallanas et al, 2007).…”

Section: Discussionmentioning

confidence: 87%

“…YAP-1 functions as a co-activator of p73 (Basu et al, 2003). The role of YAP-1 in the process of tumorigenesis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…A potential acetylation of KDKK motif in EGR-1 is YAP-1 functions as a co-activator with EGR-1 M Zagurovskaya et al required for its interaction with p300 (Matheny et al, 1994). YAP-1, a WW domain-containing protein, by binding to p73 recruits p300 to p73 target genes, leading to the induction of these genes (Basu et al, 2003). We reasoned that a similar mechanism might be responsible for recruitment of YAP-1 and p300 to the EGR-1-binding sites.…”

Section: Egr-1 Induces the Expression Of Baxmentioning

confidence: 99%

“…A differentially spliced isoform of YAP-1, with two WW domains known as YAP-2 also exists (Sudol et al, 1995). Phosphorylation of YAP by Akt or Lats1 attenuates the p73-mediated transcriptional activity and apoptosis (Basu et al, 2003;Oka et al, 2008). Whether EGR-1, like p73, is regulated through a similar interaction is not known.…”

Section: Introductionmentioning

confidence: 99%

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EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

et al. 2009

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In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/ lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1.

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Section: Discussionmentioning

confidence: 87%

“…YAP-1 functions as a co-activator of p73 (Basu et al, 2003). The role of YAP-1 in the process of tumorigenesis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Section: Egr-1 Induces the Expression Of Baxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

et al. 2009

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“…It has been demonstrated that Akt can phosphorylate YAP at serine 127 [34], leading to the translocation of YAP to the cytoplasm from the nucleus, in which it functions as a coactivator of transcription factors, including p73. To identify the signal involved in the downregulation of NLRC4, we hypothesized that the inositide phosphate phosphatase SopB, which is produced by Salmonella , may promote YAP phosphorylation through Akt in infected B cells.…”

Section: Resultsmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.

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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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Akt Phosphorylates the Yes-Associated Protein, YAP, to Induce Interaction with 14-3-3 and Attenuation of p73-Mediated Apoptosis

Cited by 741 publications

References 38 publications

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

YAPping about and not forgetting TAZ

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