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Here, the authors discover SAV1-mediated inhibition of the PP2A (zeige PPP2R4 Proteine) complex STRIPAK(SLMAP (zeige SLMAP Proteine)) as a key mechanism of MST1 (zeige MST1 Proteine)/2 activation.
WW45 has suppressive roles in lung cancer through a pathway involving Hedgehog (zeige SHH Proteine)/Gli1 (zeige GLI1 Proteine) signaling.
SAV1 represses the activation of the Akt-mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells.
using an Mst2 (zeige STK3 Proteine) mutation that disrupts homotypic dimerization, we showed that the monomeric Mst2 (zeige STK3 Proteine)-SARAH domain could form a stable complex of 1:1 stoichiometric ratio with WW45 refolded under acidic pH.
MST1/2-SAV1 associates with the NPHP transition-zone complex, promoting ciliary localization of multiple ciliary cargoes.
Mst2 (zeige STK3 Proteine) and the Ser (zeige SIGLEC1 Proteine)-3 residue of human WW45 function independently of each other in the regulation of the stability of human WW45.
We also confirmed the interaction of HAX-1 (zeige HAX1 Proteine) and hSav1 in mammalian cells.
downregulation of SAV1 and the consequent YAP1 (zeige YAP1 Proteine) activation are involved in the pathogenesis of high-grade clear cell renal cell carcinoma (zeige MOK Proteine).
MST (zeige MAP3K10 Proteine) and hSAV act as novel co-regulators of ERalpha (zeige ESR1 Proteine) and may play an important role in breast cancer pathogenesis.
hSav1 interacts with HAX1 (zeige HAX1 Proteine) and attenuates its protective role against apoptosis in MCF-7 breast cancer cells.
deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls
Loss of Sav1 induced Stat3 (zeige STAT3 Proteine) activation and a senescence-associated secretory phenotype (SASP (zeige ASPRV1 Proteine)) that coincided with the development of tubulointerstitial fibrosis.
Differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1.
In this study, they investigated epigenetic characteristics of WW45+/- mice, evaluating time-dependent changes from prior to the onset of tumorigenesis to hepatocarcinoma.
show that mice with liver-specific ablation of WW45 (a homolog of Drosophila Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas.
show using a conditional allele of sav1, that an adaptor that potentiates mst1 (zeige MST1 Proteine) and mst2 (zeige STK3 Proteine) activity is likewise required to suppress growth in the mature liver and to prevent tumor formation.
While typical WW domains function as monomeric modules that recognize proline-rich sequences, by using conserved residues that are solvent-exposed on the surface of the beta-sheet, this WW domain buries these residues in the dimer interface.
Mice lacking WW45 reveal a crucial role for WW45 in cell-cycle exit and epithelial terminal differentiation.
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein with two WW domains, a SARAH domain, and a coiled-coil region and is ubiquitously expressed in adult tissues. This protein binds to MST1 (mammalian sterile 20-like kinase 1) and promotes MST1-induced apoptosis. It has also been shown to bind to HAX1 (hematopoietic cell-specific protein 1 (HS1)-associated protein X-1) and to attenuate the anti-apoptotic effects of HAX1. Studies in human and mouse suggest this gene acts as a tumor suppressor.
, 45 kDa WW domain protein
, WW domain-containing
, protein salvador homolog 1
, WW domain-containing protein 3
, WW domain-containing protein 4
, Salvador homolog 1 protein