Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc

Peng, Hui; Slattery, Matthew; Mann, Richard S.

doi:10.1101/gad.1820009

Cited by 190 publications

(266 citation statements)

References 59 publications

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“…Several transcription factors have been shown to control tissue growth in conjunction with Yki but how these proteins regulate transcription is still unclear. [15][16][17][18] What is better defined is the mechanism by which Yki activity is regulated by the SWH pathway; Wts/LATS1/2-mediated phosphorylation of Yki/YAP results in 14-3-3-dependent cytoplasmic sequestration of Yki/YAP, thus preventing Yki/ YAP activity in the nucleus. 3 To investigate whether Wbp2 affected Yki by influencing SWH pathway-mediated repression, we determined whether Wbp2 influenced Wts-dependent phosphorylation of Yki in S2 cells using anti-phospho-Yki-S168 antibody.…”

Section: Resultsmentioning

confidence: 99%

“…14 Yki drives a growth-regulatory transcriptional programme by regulating transcription factors that include Scalloped (Sd), [15][16][17] Homothorax (Hth) and Teashirt (Tsh). 18 Yki and YAP bind via a region of B100 amino acids in their N-termini to Sd and TEAD1-4, respectively. 15,19 Additional transcription factors have been shown to be activated by YAP including pEBP2a, ErbB-4 and p73, and these factors bind to the WW domains of YAP via PPxY (PY) motifs.…”

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confidence: 99%

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Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador–Warts–Hippo pathway

et al. 2011

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The Salvador-Warts-Hippo (SWH) pathway is a key controller of tissue growth in both flies and mammals, and deregulation of pathway activity contributes to tumour formation. The SWH pathway regulates cell growth, proliferation and apoptosis by restricting activity of the Yorkie transcriptional co-activator protein. The proteins that function together with Yorkie to drive transcription and tissue growth are beginning to be revealed and include the Scalloped (Sd), Teashirt (Tsh) and Homothorax (Hth) transcription factors. In this study, we define Wbp2 as a promoter of Yorkie-dependent growth of Drosophila melanogaster tissues. Mammalian WBP2 was previously identified as a protein that interacts with the mammalian Yorkie homologue, Yes-associated protein. WBP2 has been shown to enhance steroid hormone-dependent transcription in cultured cells but its in vivo function has remained obscure. We show that D. melanogaster Wbp2 interacts with Yorkie in a WW domain-and PY motif-dependent manner and that Wbp2 can enhance Yorkie's transcriptional co-activator properties. In vivo, Wbp2 is required for growth of the D. melanogaster wing, and reduction of Wbp2 expression suppresses overgrowth of tissues that lack the warts growth-suppressive gene. Collectively, these studies define an important role for Wbp2 as a downstream component of the SWH tissue growth-control pathway.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador–Warts–Hippo pathway

et al. 2011

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“…The complexity of bantam control also highlights differential transcription factor interactions with Yorkie in growth control. While the TEAD family transcription factor Scalloped functions with Yorkie to regulate growth in the wing, recent studies have shown that the TALE family transcription factor Homothorax, together with the Zn finger transcription factor Teashirt, function with Yorkie to regulate growth in the fly eye disc 78 .…”

Section: Bountiful Crosstalk In the Hippo Pathwaymentioning

confidence: 99%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

145

106

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Signal transduction pathways interact at various levels in defining tissue morphology, size and differentiation during development. Understanding of the mechanisms by which these pathways collude has been greatly enhanced by recent insights into how shared components are independently regulated and how the activity of one system is contextualized by others. Traditionally, the components of signalling pathways have been assumed to show pathway fidelity and to act with a high degree of autonomy. However, as illustrated by the Wnt and Hippo pathways, there is increasing evidence that components are often shared between multiple pathways and other components talk to each other through multiple mechanisms.

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“…Phosphorylation of Yki results in its retention in the cytoplasm, thus blocking its transcriptional activity. 9 When Hippo signaling is inactive, Yki localizes to the nucleus where it forms complexes with transcription factors such as Scalloped, [10][11][12] Homothorax 13 or Mad 14 to activate the expression of target genes that promote cell growth, survival and proliferation. 15 Yki therefore acts as a growth promoter, whereas Hpo, Wts, Mats and Sav are considered tumor suppressors.…”

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confidence: 99%

The Hippo pathway promotes cell survival in response to chemical stress

Cara

Maile²,

Parsons

et al. 2015

Cell Death Differ

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Cellular stress defense mechanisms have evolved to maintain homeostasis in response to a broad variety of environmental challenges. Stress signaling pathways activate multiple cellular programs that range from the activation of survival pathways to the initiation of cell death when cells are damaged beyond repair. To identify novel players acting in stress response pathways, we conducted a cell culture RNA interference (RNAi) screen using caffeine as a xenobiotic stress-inducing agent, as this compound is a well-established inducer of detoxification response pathways. Specifically, we examined how caffeine affects cell survival when Drosophila kinases and phosphatases were depleted via RNAi. Using this approach, we identified and validated 10 kinases and 4 phosphatases that are essential for cell survival under caffeine-induced stress both in cell culture and living flies. Remarkably, our screen yielded an enrichment of Hippo pathway components, indicating that this pathway regulates cellular stress responses. Indeed, we show that the Hippo pathway acts as a potent repressor of stress-induced cell death. Further, we demonstrate that Hippo activation is necessary to inhibit a pro-apoptotic program triggered by the interaction of the transcriptional co-activator Yki with the transcription factor p53 in response to a range of stress stimuli. Our in vitro and in vivo loss-of-function data therefore implicate Hippo signaling in the transduction of cellular survival signals in response to chemical stress. Throughout their lives, organisms are exposed to a wide range of harmful substances. These compounds, often referred to as xenobiotics, may enter the body through direct contact, inhalation or ingestion, and can originate from many sources including pharmaceuticals, pesticides, plant toxins and pollutants. The ubiquitous and varied nature of xenobiotic pressure is reflected in the complexity of conserved cellular defense mechanisms that respond to these chemical compounds, and metazoans have thus developed a range of pathways that activate survival responses or trigger programmed cell death to eliminate damaged cells. 1 Xenobiotic pathways control the expression and activation of heat shock proteins, oxidative stress components, DNA repair enzymes, hypoxia response factors and several groups of xenobiotic-metabolizing enzymes. In eukaryotes, environmental challenges that activate stress response programs are relayed through a complex signaling cascade. Some stress pathways respond to very specific compounds, whereas others, such as those depending on Mitogen-activated protein kinases, propagate stress signals from a broad spectrum of stimuli. 1-3 Despite the importance that stress response pathways play in pharmacology and toxicology, we still have a relatively poor understanding of the complex networks that launch these cellular defense systems.We performed a quantitative cell-culture RNA interference (RNAi) assay of Drosophila kinases and phosphatases to identify key regulators of stress response pathways that reac...

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Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc

Cited by 190 publications

References 59 publications

Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador–Warts–Hippo pathway

Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador–Warts–Hippo pathway

When pathways collide: collaboration and connivance among signalling proteins in development

The Hippo pathway promotes cell survival in response to chemical stress

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