Affinage

SAV1

Protein salvador homolog 1 · UniProt Q9H4B6

Length
383 aa
Mass
44.6 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAV1 (WW45/Salvador) is a scaffold/adaptor protein that activates the Hippo tumor-suppressor pathway to enforce cell-cycle exit, apoptosis, and terminal differentiation, restraining tissue overgrowth (PMID:12202036, PMID:18369314, PMID:20404163). It was first defined genetically in Drosophila as a two-WW-domain protein that binds the Warts (LATS) kinase, and loss of Salvador elevates Cyclin E and the apoptosis inhibitor DIAP1 (PMID:12202036). SAV1 functions within a Hippo (MST1/2)–Salvador–Warts (LATS) module: MST/Hippo binds a regulatory region of SAV1 through their SARAH domains, an interaction required for kinase function (PMID:14502294, PMID:14502295, PMID:29519817), and structural work shows the SAV1 SARAH domain carries a unique folded N-terminal extension that expands the MST interface (PMID:29519817). SAV1 promotes MST activation by multiple mechanisms — a domain-swapped WW-tandem homodimer assembles an MST–SAV1 heterotetramer enabling MST trans-autophosphorylation (PMID:32905778), and SAV1 directly binds and inhibits the PP2A-containing STRIPAK(SLMAP) complex that would otherwise dephosphorylate the MST activation loop (PMID:29063833). This protection is reciprocally antagonized by the STRIPAK kinase STK25, which phosphorylates SAV1 and blocks its inhibition of STRIPAK, gating Hippo initiation (PMID:32292165). SAV1-mediated MST activation drives LATS1/2-dependent YAP/TAZ phosphorylation and cytoplasmic sequestration; genetic ablation of SAV1 in mouse liver and kidney elevates nuclear YAP/TAZ and causes overgrowth, hepatoma, fibrosis, and senescence-associated phenotypes (PMID:18369314, PMID:20404163, PMID:27550469, PMID:28320873). SAV1 is an unstable protein stabilized by MST binding and by antagonism of the HECT ligase Herc4/HERC4, and its levels are further controlled by phosphorylation-coupled degradation via GRK2 (PMID:14502295, PMID:26125558, PMID:38486990). Beyond Hippo, SAV1 has independent roles: it blocks Akt membrane recruitment by binding the Akt PH domain (PMID:30944303), promotes Gli1 ubiquitination to suppress Hedgehog signaling (PMID:27661123), stabilizes PPARγ to support adipogenesis (PMID:22292086), and with MST1/2 promotes ciliogenesis (PMID:25367221). The adhesion molecule KIRREL1 recruits SAV1 to cell-cell contacts as a feedback input to Hippo signaling (PMID:35177623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Established SAV1/Salvador as a growth-suppressing adaptor by showing it binds the Warts/LATS kinase and that its loss drives proliferation and blocks apoptosis, defining the founding genetic role.

    Evidence Genetic loss-of-function screen with binding assays and in vivo phenotypes in Drosophila

    PMID:12202036

    Open questions at the time
    • Did not define how Salvador couples to upstream kinases
    • Mammalian function not yet addressed
  2. 2003 High

    Placed Salvador in a Hippo–Salvador–Warts module by showing MST/Hippo binds Salvador via SARAH domains and directly phosphorylates it, and that Salvador is an unstable protein stabilized by Hippo binding.

    Evidence Co-IP, SARAH-domain mapping, in vitro kinase assays, genetic epistasis, and cross-species rescue in Drosophila/human cells

    PMID:12941273 PMID:14502294 PMID:14502295

    Open questions at the time
    • Structural basis of the SARAH interaction not resolved
    • Mechanism of Salvador instability not defined
  3. 2007 High

    Showed SAV1 acts within a higher-order MST2 activation complex in human cells, linking it to RASSF1A and LATS1 and to mitotic structures, and that it promotes MST2 autophosphorylation.

    Evidence Reciprocal Co-IP, immunofluorescence localization, in vitro kinase assays, and domain-deletion mapping in human cells

    PMID:17379520

    Open questions at the time
    • Stoichiometry of the complex not resolved
    • Did not establish how SAV1 activates MST2 mechanistically
  4. 2008 High

    Defined the mammalian physiological output: SAV1 is required for MST1 activation and LATS1/2-dependent YAP phosphorylation, driving cell-cycle exit and terminal differentiation of epithelial progenitors.

    Evidence Conditional knockout mice with pathway readouts by IF, IP, and western blot

    PMID:18369314

    Open questions at the time
    • Tissue-specific contributions not fully mapped
    • Did not address Hippo-independent functions
  5. 2010 High

    Demonstrated SAV1 is a tumor suppressor in vivo: liver-specific loss expands oval cells, elevates nuclear YAP, and produces hepatoma.

    Evidence Liver-specific conditional knockout mice with IHC, IF, and western blot

    PMID:20404163

    Open questions at the time
    • Cell-of-origin for the tumors not fully defined
    • Did not test reversibility upon YAP inhibition
  6. 2011 Medium

    Identified Hippo-independent and self-association determinants: MST2 phosphorylates SAV1 at four residues controlling dimerization and cell death, and SAV1 supports RASSF1A/p73 apoptosis without canonical MST activation.

    Evidence MS phospho-mapping, mutagenesis, Co-IP, and apoptosis/cell-cycle assays in human cells

    PMID:21489991 PMID:21944251

    Open questions at the time
    • Single-lab phospho-site assignments
    • Hippo-independent apoptotic mechanism not biochemically resolved
  7. 2012 Medium

    Extended SAV1 function beyond growth control by showing WW-domain-mediated binding to PPARγ stabilizes it and supports adipocyte differentiation.

    Evidence Co-IP, domain mapping, siRNA, luciferase reporter, and adipogenesis assays in 3T3-L1 cells

    PMID:22292086

    Open questions at the time
    • In vivo relevance to adipogenesis not established
    • Single lab
  8. 2013 High

    Revealed upstream regulation of the Hippo-Salvador interaction: Par-1 phosphorylates Hippo and disrupts Hpo-Sav association, destabilizing Salvador.

    Evidence Co-IP, in vitro kinase assay, and genetic epistasis in Drosophila with mammalian validation

    PMID:23940457

    Open questions at the time
    • Conditions selecting Par-1 regulation in mammals not defined
  9. 2014 High

    Connected the MST1/2-SAV1 complex to ciliogenesis via AURKA phosphorylation and NPHP transition-zone association, broadening SAV1's organelle-level roles.

    Evidence Co-IP, in vitro kinase assay, localization, and LOF in cultured cells and zebrafish

    PMID:25367221

    Open questions at the time
    • SAV1's specific contribution versus MST1/2 not separated
    • Link to canonical Hippo output not addressed
  10. 2015 Medium

    Defined a positive-feedback stability mechanism: Hippo kinase antagonizes the HECT ligase Herc4, protecting Salvador from ubiquitin-dependent degradation.

    Evidence RNAi screen, Co-IP, ubiquitylation, and genetic interaction in Drosophila

    PMID:26125558

    Open questions at the time
    • Human HERC4 regulation of SAV1 not directly tested
    • Single lab, Drosophila system
  11. 2016 Medium

    Showed a Hippo-independent suppressive role on Hedgehog signaling: SAV1 binds Gli1 and promotes its ubiquitination to repress Gli1 target genes.

    Evidence MS interaction ID, Co-IP, ubiquitination, reporter assays, and LOF/GOF in lung cancer cells

    PMID:27661123

    Open questions at the time
    • E3 ligase mediating Gli1 ubiquitination not identified
    • Single lab
  12. 2017 High

    Provided the structural and biochemical mechanism of MST activation: a SAV1 SARAH heterodimer and WW-domain-driven heterotetramer enable MST2 trans-autophosphorylation, while SAV1 directly inhibits STRIPAK(SLMAP) to protect the MST2 activation loop.

    Evidence Crystal structure, reconstitution, phosphatase assay, Co-IP, CRISPR knockout, and mutagenesis

    PMID:29063833

    Open questions at the time
    • How STRIPAK recruitment is dynamically regulated in cells not resolved at the time
  13. 2017 Medium

    Established disease relevance of SAV1 loss in kidney: epithelial Sav1 deletion activates TAZ, TGF-β, β-catenin, Stat3, senescence, and SASP, driving tubulointerstitial fibrosis.

    Evidence Conditional knockout mice, fibrosis model, reporter assays, siRNA, and verteporfin rescue

    PMID:27550469 PMID:28320873

    Open questions at the time
    • Direct versus indirect transcriptional effects not fully separated
    • Single lab per study
  14. 2018 High

    Resolved the structural basis of the Salvador-Hippo SARAH interface, showing a unique Salvador N-terminal extension expands and strengthens the interaction and competes with RassF binding.

    Evidence X-ray crystallography, cross-linked MS, co-transfection western blot, and in vitro kinase assay

    PMID:29519817

    Open questions at the time
    • Reconciliation of cellular activation with in vitro inhibition by isolated SARAH not resolved
  15. 2019 Medium

    Defined a Hippo-independent SAV1 function in PI3K/Akt control: SAV1 binds the Akt PH domain to block membrane recruitment, with MERTK-driven Akt phosphorylation releasing SAV1.

    Evidence Co-IP, domain mapping, phospho-westerns, fractionation, mutagenesis, and cancer-mutation analysis

    PMID:30944303

    Open questions at the time
    • Structural basis of SAV1-PH binding not solved
    • Single lab
  16. 2020 High

    Established mutual antagonism gating Hippo initiation: STRIPAK kinase STK25 phosphorylates SAV1 to disable its STRIPAK inhibition, balancing MST2 activation.

    Evidence In vitro kinase assay, Co-IP, siRNA, and MST2 phospho-westerns extending the prior structural study

    PMID:32292165

    Open questions at the time
    • SAV1 phospho-sites targeted by STK25 not fully mapped
    • Single lab
  17. 2020 High

    Defined the molecular architecture of SAV1 self-association: the WW-tandem plus Pro-rich extension forms a domain-swapped homodimer required for MST/SAV1 complex assembly and kinase activation, with cancer variants disrupting the dimer.

    Evidence X-ray crystallography, binding assays, mutagenesis, Co-IP, and kinase activation assay

    PMID:32905778

    Open questions at the time
    • In vivo consequences of dimer-disrupting variants not tested
  18. 2022 Medium

    Identified a spatial feedback input: the adhesion molecule KIRREL1 recruits SAV1 to cell-cell contacts, restraining YAP in neighboring cells and modulating liver regeneration.

    Evidence Co-IP, live-cell imaging, CRISPR KO, YAP reporter, and mouse liver regeneration model

    PMID:35177623

    Open questions at the time
    • How KIRREL1-bound SAV1 mechanistically engages MST not defined
    • Single lab
  19. 2023 Medium

    Linked GPCR signaling to SAV1 turnover: GRK2 phosphorylates, ubiquitinates, and degrades SAV1, releasing YAP in synoviocytes and contributing to rheumatoid arthritis pathology.

    Evidence Co-IP, ubiquitination assay, siRNA, paroxetine inhibition, and rat arthritis model

    PMID:38486990

    Open questions at the time
    • GRK2 phospho-sites on SAV1 not mapped
    • E3 ligase coupling not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SAV1's multiple Hippo-independent activities (Akt, Hedgehog/Gli1, PPARγ, ciliogenesis) are coordinated with its core MST-activating scaffold function, and which inputs select among them, remains unresolved.
  • No unifying mechanism integrating Hippo and non-Hippo roles
  • Structural models for non-Hippo partner interactions lacking
  • Tissue-specific partner selection undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
GRK2KIRREL1LATS1MST1MST2RASSF1ASLMAPSTK25
Complex memberships
MST1/2-SAV1 complexRASSF1A-MST2-WW45-LATS1 complexSTRIPAK (as inhibitory target)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Salvador (SAV1/WW45) contains two WW domains and directly binds to the Warts (LATS) protein kinase, promoting both cell cycle exit and apoptosis in Drosophila; loss of sav results in elevated Cyclin E and DIAP1 levels. Genetic loss-of-function screen, co-immunoprecipitation/binding assay, in vivo phenotypic analysis Cell High 12202036
2003 Hippo (Drosophila MST1/2 ortholog) binds to a regulatory domain of Salvador (Sav) through its SARAH domain; this interaction is essential for Hippo kinase function and for the Hpo-Sav-Wts signaling module that coordinately regulates cell proliferation and apoptosis. Co-immunoprecipitation, genetic epistasis, dominant-negative and gain-of-function experiments in Drosophila Nature Cell Biology High 14502294 14502295
2003 Hippo (Drosophila MST1/2) phosphorylates DIAP1 in a Hpo-dependent manner in S2 cells and can phosphorylate DIAP1 in vitro; Sav is an unstable protein that is stabilized by Hpo binding. In vitro kinase assay, S2 cell phosphorylation assay, co-expression stabilization experiments Nature Cell Biology Medium 14502295
2003 Hippo (Hpo) kinase phosphorylates Salvador (Sav) directly; hpo, sav, and wts define a genetic pathway that regulates diap1 at the transcriptional level; human MST2 (hpo homolog) completely rescues Drosophila hpo mutant overgrowth. In vitro kinase assay, genetic epistasis, cross-species rescue experiment Cell High 12941273
2007 RASSF1A, MST2, WW45 (SAV1), and LATS1 form a complex in human cells; MST2 enhances the RASSF1A-WW45 interaction, which requires the C-terminal SARAH domain of both proteins; the complex localizes to centrosomes and spindle poles through mitosis and to the midbody during cytokinesis; RASSF1A and WW45 activate MST2 by promoting MST2 autophosphorylation and LATS1 phosphorylation. Co-immunoprecipitation, immunofluorescence/subcellular localization, in vitro kinase assay, domain-deletion mapping Current Biology High 17379520
2008 WW45 (SAV1) is required for MST1 activation and its translocation to the nucleus upon differentiation signal in mouse epithelial cells; WW45 mediates LATS1/2 activation downstream of MST1, leading to YAP phosphorylation and cytoplasmic translocation, resulting in cell-cycle exit and terminal differentiation of epithelial progenitors. Conditional knockout mice, immunofluorescence, immunoprecipitation, western blot for pathway activation The EMBO Journal High 18369314
2009 Human WW45 (hSAV1) physically associates with MST1 (confirmed by co-immunoprecipitation and co-localization); hWW45 is present in both cytoplasm and nucleus; hWW45 enhances MST1-induced apoptosis when co-expressed, and siRNA depletion of hWW45 suppresses MST1-induced apoptosis. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown with apoptosis readout International Journal of Molecular Medicine Medium 19212654
2010 Liver-specific ablation of WW45 (SAV1) in mice leads to increased liver size, expansion of hepatic oval cells, and eventual hepatoma; WW45 loss increases YAP abundance and promotes its nuclear localization specifically in oval cells, driving their proliferation. Liver-specific conditional knockout mice, immunofluorescence, immunohistochemistry, western blot Proceedings of the National Academy of Sciences of the United States of America High 20404163
2011 SAV1 (Salvador) promotes apoptosis in human cells and interacts with RASSF1A; RASSF1A requires Salvador for full apoptotic activity and to activate p73; this effect does not require direct MST kinase activation or canonical Hippo pathway signaling, indicating SAV1 has Hippo pathway-independent functions. Co-immunoprecipitation, siRNA knockdown, apoptosis assays, cell cycle analysis, transformation assays The Journal of Biological Chemistry Medium 21489991
2011 MST2-mediated phosphorylation of SAV1 at Thr-26, Ser-27, Ser-36, and Ser-269 promotes cell death; mutation of all four residues (SAV1-4A) weakens SAV1 interaction with MST2, reduces SAV1 self-dimerization, and inhibits MST2- and K-RasG12V-induced cell death. Mass spectrometric phosphorylation mapping, site-directed mutagenesis, co-immunoprecipitation, cell death assays BMB Reports Medium 21944251
2012 MST2 stimulates binding of SAV1 to PPARγ via the WW domains of SAV1 and PPYY motif of PPARγ; SAV1 stabilizes PPARγ protein and increases PPARγ transactivation; SAV1 knockdown decreases PPARγ levels in 3T3-L1 adipocytes and impairs adipocyte differentiation. Co-immunoprecipitation, domain deletion/mutation analysis, siRNA knockdown, luciferase reporter assay, western blot PLoS One Medium 22292086
2013 Par-1 kinase physically interacts with both Hippo (Hpo) and Salvador (Sav) in Drosophila; Par-1 phosphorylates Hpo at Ser30, restricting its activity; Par-1 inhibits Hpo-Sav association, resulting in Sav dephosphorylation and destabilization; this regulation is conserved in mammalian cells. Co-immunoprecipitation, in vitro kinase assay, genetic epistasis, gain/loss-of-function in Drosophila, mammalian cell validation PLoS Biology High 23940457
2014 The MST1/2-SAV1 complex promotes ciliogenesis: MST1 activates during ciliogenesis and localizes to the basal body; MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex; MST1/2-SAV1 also associates with the NPHP transition-zone complex promoting ciliary cargo localization; depletion of MST1/2 or SAV1 impairs ciliogenesis in cultured cells and zebrafish. Co-immunoprecipitation, in vitro kinase assay, immunofluorescence/subcellular localization, siRNA knockdown, zebrafish morpholino knockdown Nature Communications High 25367221
2015 In Drosophila, Hippo kinase stabilizes its adaptor Salvador by antagonizing the HECT ubiquitin ligase Herc4; Herc4 promotes Salvador ubiquitylation and degradation; Hippo reduces Salvador/Herc4 interaction in a kinase-dependent manner, creating a positive feedback loop. RNAi screen, co-immunoprecipitation, ubiquitylation assay, genetic interaction PLoS One Medium 26125558
2016 WW45 (SAV1) interacts with Gli1; WW45 promotes Gli1 ubiquitination and inhibits expression of Gli1 target genes, thereby negatively regulating Hedgehog signaling in lung cancer cells independently of canonical Hippo pathway activity. Mass spectrometry (binding partner identification), co-immunoprecipitation, ubiquitination assay, luciferase reporter assay, siRNA and overexpression functional studies Oncotarget Medium 27661123
2017 SAV1 promotes MST1/2 activation by directly binding to and inhibiting the PP2A complex STRIPAK(SLMAP), protecting MST2 activation-loop phosphorylation; SAV1 and MST2 heterodimerize through their SARAH domains; two SAV1-MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer enabling MST2 trans-autophosphorylation; SLMAP binds autophosphorylated MST2 linker, recruits STRIPAK, and promotes PP2A-mediated dephosphorylation of MST2 activation loop; genetic ablation of SLMAP in human cells leads to spontaneous Hippo pathway activation and alleviates the need for SAV1. Crystal structure, biochemical reconstitution, in vitro phosphatase assay, co-immunoprecipitation, CRISPR/Cas9 knockout, mutagenesis eLife High 29063833
2017 Tubular epithelial cell-specific deletion of Sav1 in mice leads to tubulointerstitial fibrosis; Sav1 depletion increases TGF-β and activates β-catenin; TAZ (downstream Hippo effector) is significantly activated in Sav1-knockout mice; in vitro, TAZ directly regulates TGF-β and TGF-β receptor II expression. Conditional knockout mice, western blot, luciferase reporter assay, siRNA knockdown, in vivo fibrosis model (UUO) Scientific Reports Medium 27550469
2017 Sav1 loss in mouse renal epithelium induces Stat3 activation and a senescence-associated secretory phenotype (SASP) coinciding with tubulointerstitial fibrosis; YAP inhibition with verteporfin inhibits senescence, SASP, and Stat3 activation downstream of Sav1 loss. Conditional knockout mice, western blot, pharmacological inhibition (verteporfin), gene expression analysis Molecular and Cellular Biology Medium 28320873
2018 Crystal structure of Drosophila Salvador (Sav) and Hippo (Hpo) SARAH domains in complex reveals that Salvador SARAH domain has a folded N-terminal extension that expands the binding interface with Hpo and is unique to Salvador; this extension enhances binding affinity and is required for proper Hippo kinase modulation; Salvador/Sav SARAH domain interaction with Hippo/Hpo is mutually exclusive with dRassF/Hippo SARAH domain interaction; human Salvador increases MST2 autophosphorylation in cells, but isolated Salvador SARAH domain inhibits MST2 autophosphorylation in vitro. X-ray crystallography, cross-linked mass spectrometry, co-transfection with western blot, in vitro kinase assay The Journal of Biological Chemistry High 29519817
2019 SAV1 inhibits Akt activation independently of its Hippo pathway role by binding to a proline-tyrosine motif in the Akt-PH domain, blocking Akt movement to the plasma membrane; MERTK phosphorylates Akt1 at Y26, releasing SAV1 binding and enabling Akt plasma membrane recruitment and activation; cancer-associated SAV1 mutations impair SAV1-Akt binding leading to Akt hyperactivation. Co-immunoprecipitation, domain mapping, phospho-specific western blot, subcellular fractionation/localization, site-directed mutagenesis, cancer mutation analysis Nature Communications Medium 30944303
2020 The GCKIII kinase STK25 (a STRIPAK component) directly phosphorylates SAV1 and diminishes SAV1's ability to inhibit STRIPAK, thereby promoting STRIPAK-mediated inhibition of MST2; depletion of STK25 enhances MST2 activation without affecting STRIPAK(SLMAP) integrity, establishing a mutual antagonism between STRIPAK and SAV1 that controls Hippo pathway initiation. In vitro kinase assay, co-immunoprecipitation, siRNA knockdown, western blot for MST2 phosphorylation eLife High 32292165
2020 SAV1 WW tandem with its short Pro-rich extension (WW12ex) forms a domain-swapped homodimer; the crystal structure reveals that the Pro-rich extension of one subunit binds to both WW domains of the other subunit; SAV1 WW12ex-mediated dimerization is required for MST/SAV1 complex assembly and MST kinase activation; several cancer-related SAV1 variants disrupt dimer formation. X-ray crystallography, biochemical binding assays, mutagenesis, co-immunoprecipitation, kinase activation assay Cell Reports High 32905778
2022 The cell adhesion molecule KIRREL1 physically interacts with SAV1 and recruits SAV1 to cell-cell contact sites; KIRREL1 knockout increases YAP activity in neighboring cells; in mouse liver regeneration, KIRREL1 upregulation enhances Hippo signaling and its ablation increases hepatic YAP activity. Co-immunoprecipitation, live-cell imaging/localization, CRISPR/KO, YAP reporter assay, mouse liver regeneration model Nature Communications Medium 35177623
2023 GRK2 phosphorylates, ubiquitinates, and promotes degradation of SAV1 in fibroblast-like synoviocytes (FLSs); GRK2 is upregulated by GPCR agonists such as prostaglandin E2 (PGE2) in rheumatoid arthritis; SAV1 degradation by GRK2 leads to decreased YAP phosphorylation, nuclear YAP accumulation, and aberrant FLS proliferation; GRK2 depletion or inhibition with paroxetine rescues SAV1 expression and YAP phosphorylation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, pharmacological inhibition (paroxetine), western blot, in vivo rat arthritis model Acta Pharmaceutica Sinica B Medium 38486990

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 946 12941273
2002 salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 735 12202036
2003 Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nature cell biology 658 14502294
2007 The Salvador-Warts-Hippo pathway - an emerging tumour-suppressor network. Nature reviews. Cancer 558 17318211
2003 The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nature cell biology 493 14502295
2010 The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 406 20404163
2010 Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Developmental cell 329 20159599
2010 Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Current biology : CB 289 20362447
2006 Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Current biology : CB 273 17045801
2010 Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Current biology : CB 266 20362445
2011 Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. Developmental cell 202 22075147
2012 Decreased kidney function among agricultural workers in El Salvador. American journal of kidney diseases : the official journal of the National Kidney Foundation 193 22300650
2011 The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Developmental cell 190 22075148
2007 RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Current biology : CB 170 17379520
2017 High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks. mBio 164 29138300
2008 A crucial role of WW45 in developing epithelial tissues in the mouse. The EMBO journal 164 18369314
2007 Salvador-warts-hippo signaling promotes Drosophila posterior follicle cell maturation downstream of notch. Current biology : CB 122 17964162
2017 SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. eLife 119 29063833
2010 The Salvador/Warts/Hippo pathway controls regenerative tissue growth in Drosophila melanogaster. Developmental biology 106 21111727
2007 The salvador-warts-hippo pathway is required for epithelial proliferation and axis specification in Drosophila. Current biology : CB 90 17964161
2009 Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines. Cancer research 74 19584286
2014 The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nature communications 71 25367221
2000 Acute lymphoblastic leukemia in a developing country: preliminary results of a nonrandomized clinical trial in El Salvador. Journal of pediatric hematology/oncology 70 11132215
2016 The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis. Scientific reports 66 27550469
2011 Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma. BMC cancer 65 22185343
2014 Acceptability of self-collected versus provider-collected sampling for HPV DNA testing among women in rural El Salvador. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 59 24880188
2011 Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador-Warts-Hippo pathway. Cell death and differentiation 59 21311569
2013 Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association. PLoS biology 58 23940457
2007 Adenoviruses associated with acute gastroenteritis in hospitalized and community children up to 5 years old in Rio de Janeiro and Salvador, Brazil. Journal of medical microbiology 52 17314359
2002 Statistical and algorithmic methods for fluctuation analysis with SALVADOR as an implementation. Mathematical biosciences 51 11916511
2007 Tissue tropism of salmonid alphaviruses (subtypes SAV1 and SAV3) in experimentally challenged Atlantic salmon (Salmo salar L.). Archives of virology 47 17578649
2000 Effect of malnutrition at the time of diagnosis on the survival of children treated for cancer in El Salvador and Northern Brazil. Journal of pediatric hematology/oncology 47 11132216
2011 Frequent epigenetic inactivation of KIBRA, an upstream member of the Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia. Epigenetics 43 21173572
2019 Oropouche Virus Detection in Febrile Patients' Saliva and Urine Samples in Salvador, Bahia, Brazil. Japanese journal of infectious diseases 41 31787741
2005 Hemoglobinopathies in newborns from Salvador, Bahia, Northeast Brazil. Cadernos de saude publica 41 15692663
2005 Infective dermatitis associated with the human T cell lymphotropic virus type I in Salvador, Bahia, Brazil. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 40 15889351
2020 STK25 suppresses Hippo signaling by regulating SAV1-STRIPAK antagonism. eLife 39 32292165
2015 The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador. International journal of cancer 38 25639903
2017 The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma. Oncotarget 37 28938586
2019 MERTK mediated novel site Akt phosphorylation alleviates SAV1 suppression. Nature communications 35 30944303
2016 Kidney-specific knockout of Sav1 in the mouse promotes hyperproliferation of renal tubular epithelium through suppression of the Hippo pathway. The Journal of pathology 34 26913567
2016 The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the Prehierarchical Follicles in Hen Ovary. PloS one 33 27505353
2010 Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway. Fly 33 20798605
2004 Childhood anemia prevalence and associated factors in Salvador, Bahia, Brazil. Cadernos de saude publica 33 15608866
2003 BetaS-haplotypes in sickle cell anemia patients from Salvador, Bahia, Northeastern Brazil. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 33 14502357
2017 Sav1 Loss Induces Senescence and Stat3 Activation Coinciding with Tubulointerstitial Fibrosis. Molecular and cellular biology 32 28320873
2011 Salvador protein is a tumor suppressor effector of RASSF1A with hippo pathway-independent functions. The Journal of biological chemistry 32 21489991
2022 Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites. Nature communications 31 35177623
2013 Urban population genetics of slum-dwelling rats (Rattus norvegicus) in Salvador, Brazil. Molecular ecology 30 24118116
2010 Differential requirement of Salvador-Warts-Hippo pathway members for organ size control in Drosophila melanogaster. Development (Cambridge, England) 30 20110315
2022 ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m6A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype. International journal of biological sciences 29 35414790
2012 Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPARγ. PloS one 29 22292086
2006 Prevalence of hepatitis C virus (HCV) infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 29 16648896
2019 Frailty and Its Association with Health Related Quality of Life in Older HIV Patients, in Salvador, Brazil. AIDS research and human retroviruses 28 31373215
2017 Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador. Journal of lower genital tract disease 28 27922905
2010 Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador. European journal of cancer (Oxford, England : 1990) 27 20674335
2017 SAV1 represses the development of human colorectal cancer by regulating the Akt-mTOR pathway in a YAP-dependent manner. Cell proliferation 26 28618450
2014 Serological survey of Leishmania infection in blood donors in Salvador, Northeastern Brazil. BMC infectious diseases 24 25073468
2012 HIV and STI control in El Salvador: results from an integrated behavioural survey among men who have sex with men. Sexually transmitted infections 24 22917694
2012 Validation of a food frequency questionnaire for children and adolescents aged 4 to 11 years living in Salvador, Bahia. Nutricion hospitalaria 24 23165550
2003 Globin haplotypes of human T-cell lymphotropic virus type I-infected individuals in Salvador, Bahia, Brazil, suggest a post-Columbian African origin of this virus. Journal of acquired immune deficiency syndromes (1999) 24 12869844
2020 A WW Tandem-Mediated Dimerization Mode of SAV1 Essential for Hippo Signaling. Cell reports 23 32905778
2019 The cost-effectiveness of implementing HPV testing for cervical cancer screening in El Salvador. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 23 30702142
2015 Hippo Stabilises Its Adaptor Salvador by Antagonising the HECT Ubiquitin Ligase Herc4. PloS one 23 26125558
2020 circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis. Frontiers in physiology 21 32848851
2016 Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador. Journal of lower genital tract disease 21 26890683
2015 Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring helix-loop-helix proteins. Developmental cell 21 25579975
2013 Zoonotic potential of multidrug-resistant extraintestinal pathogenic Escherichia coli obtained from healthy poultry carcasses in Salvador, Brazil. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 21 23290470
2012 Transcriptomic analysis of the host response to early stage salmonid alphavirus (SAV-1) infection in Atlantic salmon Salmo salar L. Fish & shellfish immunology 21 22365992
2010 Prevalence and genotypes of hepatitis C virus among injecting drug users from Salvador-BA, Brazil. Memorias do Instituto Oswaldo Cruz 21 20512243
2009 Mitochondrial echoes of first settlement and genetic continuity in El Salvador. PloS one 21 19724647
2016 Analysis of Liver Tumor-Prone Mouse Models of the Hippo Kinase Scaffold Proteins RASSF1A and SAV1. Cancer research 20 26980762
2010 Alloimmunization and clinical profile of sickle cell disease patients from Salvador-Brazil. Ethnicity & disease 20 20503893
2008 100% adherence study: educational workshops vs. video sessions to improve adherence among ART-naïve patients in Salvador, Brazil. AIDS and behavior 20 18512141
2008 [Acute lymphoblastic leukemia: experience in adult patients treated with hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Cohort 2003-2007]. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 20 19378832
1988 An insertion within the factor IX gene: hemophilia BEl Salvador. American journal of human genetics 19 2831715
2020 Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy. Cell death & disease 18 32439835
2018 Occurrence of Aflatoxin M1 in cow milk in El Salvador: Results from a two-year survey. Toxicology reports 18 30009135
2018 Genetic variability of the Aedes aegypti (Diptera: Culicidae) mosquito in El Salvador, vector of dengue, yellow fever, chikungunya and Zika. Parasites & vectors 18 30547835
2015 Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program. BMC public health 18 26474762
2011 Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death. BMB reports 18 21944251
2021 Emergence of MDR invasive Neisseria meningitidis in El Salvador, 2017-19. The Journal of antimicrobial chemotherapy 17 33517418
2019 SAV1, regulated by microRNA-21, suppresses tumor growth in colorectal cancer. Biochemistry and cell biology = Biochimie et biologie cellulaire 17 30681889
2011 Impact of depression on quality of life in people living with human T cell lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation 17 22109110
2009 [Assessing the insecticide resistance of an Aedes aegypti strain in El Salvador]. Revista panamericana de salud publica = Pan American journal of public health 17 20058833
2019 The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador. Preventive medicine 16 31765712
2017 Association between seroprevalence of IgG anti-Toxoplasma gondii and risk factors for infection among pregnant women in Climério de Oliveira Maternity, Salvador, Bahia, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo 16 29267598
2015 Hepatitis C virus infection and spontaneous clearance in HTLV-1 and HIV co-infected patients in Salvador, Bahia, Brazil. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 16 26254690
2011 Demand for sanitation in Salvador, Brazil: a hybrid choice approach. Social science & medicine (1982) 16 21439700
2009 The human WW45 protein enhances MST1-mediated apoptosis in vivo. International journal of molecular medicine 16 19212654
2023 GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis. Acta pharmaceutica Sinica. B 15 38486990
2012 Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway. Cells 15 24710534
2006 The genetic male legacy from El Salvador. Forensic science international 15 16916590
2003 Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia Brazil. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 15 14636481
2020 RNA-binding protein Musashi2 regulates Hippo signaling via SAV1 and MOB1 in pancreatic cancer. Medical oncology (Northwood, London, England) 14 32780197
2018 Salvador has an extended SARAH domain that mediates binding to Hippo kinase. The Journal of biological chemistry 14 29519817
2017 Protein salvador homolog 1 acts as a tumor suppressor and is modulated by hypermethylation in pancreatic ductal adenocarcinoma. Oncotarget 14 28968962
2016 WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer. Oncotarget 14 27661123
2013 Transmitted drug-resistance in human immunodeficiency virus-infected adult population in El Salvador, Central America. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 14 23782115
2007 HIV-1 seroprevalence in the general population of Salvador, Bahia State, Northeast Brazil. Cadernos de saude publica 14 17187101

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