A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis.

Abstract:

:YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. Aberrant hyperactivation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivation impairs tissue development and regeneration. Dynamic and precise control of YAP/TAZ activity is thus important to ensure proper physiological regulation and homeostasis of the cells. Here, we show that YAP/TAZ activation results in activation of their negative regulators, LATS1/2 (large tumor suppressor 1/2) kinases, to constitute a negative feedback loop of the Hippo pathway in both cultured cells and mouse tissues. YAP/TAZ in complex with the transcription factor TEAD (TEA domain family member) directly induce LATS2 expression. Furthermore, YAP/TAZ also stimulate the kinase activity of LATS1/2 through inducing NF2 (neurofibromin 2). This feedback regulation is responsible for the transient activation of YAP upon lysophosphatidic acid (LPA) stimulation and the inhibition of YAP-induced cell migration. Thus, this LATS-mediated feedback loop provides an efficient mechanism to establish the robustness and homeostasis of YAP/TAZ regulation.

journal_name

Genes Dev

journal_title

Genes & development

authors

Moroishi T,Park HW,Qin B,Chen Q,Meng Z,Plouffe SW,Taniguchi K,Yu FX,Karin M,Pan D,Guan KL

doi

10.1101/gad.262816.115

subject

Has Abstract

pub_date

2015-06-15 00:00:00

pages

1271-84

issue

12

eissn

0890-9369

issn

1549-5477

pii

29/12/1271

journal_volume

29

pub_type

杂志文章
  • Polar localization of the replication origin and terminus in Escherichia coli nucleoids during chromosome partitioning.

    abstract::We show the intracellular localization of the Escherichia coli replication origin (oriC) and chromosome terminus during the cell division cycle by FISH. In newborn cells, oriC is localized at the old-pole-proximal nucleoid border and the terminus at the new-pole-proximal nucleoid border. One copy of replicated oriC mi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.7.1036

    authors: Niki H,Hiraga S

    更新日期:1998-04-01 00:00:00

  • Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B.

    abstract::Cyclin B3 has been conserved during higher eukaryote evolution as evidenced by its identification in chicken, nematodes, and insects. We demonstrate that Cyclin B3 is present in addition to Cyclins A and B in mitotically proliferating cells and not detectable in endoreduplicating tissues of Drosophila embryos. Cyclin ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.23.3741

    authors: Jacobs HW,Knoblich JA,Lehner CF

    更新日期:1998-12-01 00:00:00

  • PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes.

    abstract::PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1323805

    authors: Yan Z,Cui K,Murray DM,Ling C,Xue Y,Gerstein A,Parsons R,Zhao K,Wang W

    更新日期:2005-07-15 00:00:00

  • A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

    abstract::We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ri...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.8.1023

    authors: Min H,Turck CW,Nikolic JM,Black DL

    更新日期:1997-04-15 00:00:00

  • Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus.

    abstract::Proliferation of pancreatic islet beta cells is an important mechanism for self-renewal and for adaptive islet expansion. Increased expression of the Ink4a/Arf locus, which encodes the cyclin-dependent kinase inhibitor p16(INK4a) and tumor suppressor p19(Arf), limits beta-cell regeneration in aging mice, but the basis...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1742509

    authors: Chen H,Gu X,Su IH,Bottino R,Contreras JL,Tarakhovsky A,Kim SK

    更新日期:2009-04-15 00:00:00

  • The Dictyostelium MAP kinase ERK2 regulates multiple, independent developmental pathways.

    abstract::We showed previously that the MAP kinase ERK2 is essential for aggregation. erk2 null cells lack cAMP stimulation of adenylyl cyclase and thus cannot relay the cAMP chemotactic signal, although the cells chemotax to cAMP (Segall et al. 1995). In this paper we have examined the role of ERK2 in controlling developmental...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.1.118

    authors: Gaskins C,Clark AM,Aubry L,Segall JE,Firtel RA

    更新日期:1996-01-01 00:00:00

  • MVH in piRNA processing and gene silencing of retrotransposons.

    abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1902110

    authors: Kuramochi-Miyagawa S,Watanabe T,Gotoh K,Takamatsu K,Chuma S,Kojima-Kita K,Shiromoto Y,Asada N,Toyoda A,Fujiyama A,Totoki Y,Shibata T,Kimura T,Nakatsuji N,Noce T,Sasaki H,Nakano T

    更新日期:2010-05-01 00:00:00

  • Involvement of the carboxyl terminus of vertebrate poly(A) polymerase in U1A autoregulation and in the coupling of splicing and polyadenylation.

    abstract::Interactions required for inhibition of poly(A) polymerase (PAP) by the U1 snRNP-specific U1A protein, a reaction whose function is to autoregulate U1A protein production, are examined. PAP inhibition requires a substrate RNA to which at least two molecules of U1A protein can bind tightly, but we demonstrate that the ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.6.761

    authors: Gunderson SI,Vagner S,Polycarpou-Schwarz M,Mattaj IW

    更新日期:1997-03-15 00:00:00

  • Short-range repression permits multiple enhancers to function autonomously within a complex promoter.

    abstract::Transcriptional repressors play a key role in establishing localized patterns of gene expression in the early Drosophila embryo. Several different modes of repression have been implicated in previous studies, including competition and direct interference with the transcription complex. Here, we present evidence for "q...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.15.1829

    authors: Gray S,Szymanski P,Levine M

    更新日期:1994-08-01 00:00:00

  • Dystrophic muscle environment induces changes in cell plasticity.

    abstract::Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.241182.114

    authors: Faralli H,Dilworth FJ

    更新日期:2014-04-15 00:00:00

  • Rpp1, an essential protein subunit of nuclear RNase P required for processing of precursor tRNA and 35S precursor rRNA in Saccharomyces cerevisiae.

    abstract::The gene for an essential protein subunit of nuclear RNase P from Saccharomyces cerevisiae has been cloned. The gene for this protein, RPP1, was identified by virtue of its homology with a human scleroderma autoimmune antigen, Rpp30, which copurifies with human RNase P. Epitope-tagged Rpp1 can be found in association ...

    journal_title:Genes & development

    pub_type: 更正并重新发布的文章,杂志文章

    doi:10.1101/gad.11.21.2926

    authors: Stolc V,Altman S

    更新日期:1997-11-01 00:00:00

  • Dynamic expression and essential functions of Hes7 in somite segmentation.

    abstract::The basic helix-loop-helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior-posterior polarity is disrupted. As a resu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.930601

    authors: Bessho Y,Sakata R,Komatsu S,Shiota K,Yamada S,Kageyama R

    更新日期:2001-10-15 00:00:00

  • Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.

    abstract::Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 a...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.23.2817

    authors: Wagner AJ,Kokontis JM,Hay N

    更新日期:1994-12-01 00:00:00

  • Heritable activity: a prion that propagates by covalent autoactivation.

    abstract::Known prions (infectious proteins) are self-propagating amyloids or conformationally altered proteins, but in theory an enzyme necessary for its own activation could also be a prion (or a gene composed of protein). We show that yeast protease B is such a prion, called [beta].[beta] is infectious, reversibly curable, a...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1115803

    authors: Roberts BT,Wickner RB

    更新日期:2003-09-01 00:00:00

  • Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila.

    abstract::Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly understood, and it is uncertain whether it is possible to obliterate CSCs with...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.171959.111

    authors: Song Y,Lu B

    更新日期:2011-12-15 00:00:00

  • The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation.

    abstract::Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.14.2153

    authors: Feng XH,Zhang Y,Wu RY,Derynck R

    更新日期:1998-07-15 00:00:00

  • Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis.

    abstract::The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.268722.115

    authors: Zeng H,Xu W

    更新日期:2015-10-15 00:00:00

  • A zinc-binding site in the largest subunit of DNA-dependent RNA polymerase is involved in enzyme assembly.

    abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.18.2439

    authors: Markov D,Naryshkina T,Mustaev A,Severinov K

    更新日期:1999-09-15 00:00:00

  • Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication.

    abstract::Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage bypass is enabled at replication stress...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.265629.115

    authors: Urulangodi M,Sebesta M,Menolfi D,Szakal B,Sollier J,Sisakova A,Krejci L,Branzei D

    更新日期:2015-10-01 00:00:00

  • The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.

    abstract::Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor format...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.191973.112

    authors: Utermark T,Rao T,Cheng H,Wang Q,Lee SH,Wang ZC,Iglehart JD,Roberts TM,Muller WJ,Zhao JJ

    更新日期:2012-07-15 00:00:00

  • ZNF445 is a primary regulator of genomic imprinting.

    abstract::Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.320069.118

    authors: Takahashi N,Coluccio A,Thorball CW,Planet E,Shi H,Offner S,Turelli P,Imbeault M,Ferguson-Smith AC,Trono D

    更新日期:2019-01-01 00:00:00

  • Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs.

    abstract::U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dom...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.5.5.773

    authors: Shannon KW,Guthrie C

    更新日期:1991-05-01 00:00:00

  • The epigenome and the mitochondrion: bioenergetics and the environment [corrected].

    abstract::In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.1960210

    authors: Wallace DC

    更新日期:2010-08-01 00:00:00

  • Selection of the initiator tRNA by Escherichia coli initiation factors.

    abstract::We have developed a new technique, called 'toeprinting,' which has allowed a study of the tRNA-binding properties of Escherichia coli translation initiation complexes. In response to natural mRNAs, the initiator tRNA and a variety of elongator tRNAs bind to the same tRNA-binding site on the 30S ribosomal subunit as lo...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.12a.1899

    authors: Hartz D,McPheeters DS,Gold L

    更新日期:1989-12-01 00:00:00

  • BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4.

    abstract::Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1682108

    authors: Furtado MB,Solloway MJ,Jones VJ,Costa MW,Biben C,Wolstein O,Preis JI,Sparrow DB,Saga Y,Dunwoodie SL,Robertson EJ,Tam PP,Harvey RP

    更新日期:2008-11-01 00:00:00

  • Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification.

    abstract::Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.307132.117

    authors: Boisclair Lachance JF,Webber JL,Hong L,Dinner AR,Rebay I

    更新日期:2018-03-01 00:00:00

  • The need for enhancers is acquired upon formation of a diploid nucleus during early mouse development.

    abstract::The activity of the polyoma virus (PyV) origin of DNA replication was used as a sensitive assay for enhancer function in one- and two-cell mouse embryos by injecting embryos with plasmid DNA containing different PyV ori configurations, allowing them to continue development in vitro, and then measuring plasmid DNA repl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.9.1115

    authors: Martínez-Salas E,Cupo DY,DePamphilis ML

    更新日期:1988-09-01 00:00:00

  • Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

    abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.18.2266

    authors: Lydon JP,DeMayo FJ,Funk CR,Mani SK,Hughes AR,Montgomery CA Jr,Shyamala G,Conneely OM,O'Malley BW

    更新日期:1995-09-15 00:00:00

  • Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

    abstract::The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a tran...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.284729.116

    authors: Bechard ME,Bankaitis ED,Hipkens SB,Ustione A,Piston DW,Yang YP,Magnuson MA,Wright CV

    更新日期:2016-08-15 00:00:00

  • Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube.

    abstract::The Wnt gene family encodes a group of cysteine-rich proteins implicated in intercellular signaling during several stages of vertebrate development. This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors. Here we describe the molecular cloning of an additional member of th...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.5.3.381

    authors: Roelink H,Nusse R

    更新日期:1991-03-01 00:00:00