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A Comparison of Ci/Gli (show GLI1 Proteins) Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog (show SHH Proteins) Response
Sufu can sequester Ci/Gli (show GLI1 Proteins) in the cytoplasm through binding to an N-terminal site while inhibiting Ci/Gli (show GLI1 Proteins) activity in the nucleus depending on a C-terminal Sufu-interacting site.
Drosophila Hedgehog (show SHH Proteins) signaling promotes downregulation of Su(fu) through its target protein HIB (Hh-induced BTB protein).
Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-nuclear localization sequence.
The 'closed' form of Sufu is stabilized by Gli (show GLI1 Proteins) binding and inhibited by Hh treatment, whereas the 'open' state of Sufu is promoted by Gli (show GLI1 Proteins)-dissociation and Hh signaling.
Su(fu) causes the Rdx (show RDX Proteins) switch between two mchanisms of Cubitus interruptus regulation.
Suppressor of Fused represses Gli (show GLI1 Proteins)-mediated transcription by recruiting the SAP18 (show SAP18 Proteins)-mSin3 corepressor complex.
Differential Hh target gene regulation can be accomplished by differential sensitivity of Cos2 and Su(Fu) to Hh.
Su(fu) protein levels and isoforms are crucial for the modulation of the different Ci states that control Hh target gene expression.
Sufu may act as a common regulator of Hh and Wnt (show WNT2 Proteins) signaling and contribute to intertwining the two pathways.
Down-regulation of microRNA-224 inhibits growth and epithelial-to-mesenchymal transition phenotype via modulating SUFU expression in bladder cancer cells.
Itch/beta-arre (show ARRB2 Proteins)stin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability.
Patients with SUFU pathogenic variants were significantly more likely to develop a medulloblastoma, a meningioma or an ovarian fibroma, but were less likely to develop a jaw cyst.
Nek2A (show NEK2 Proteins) is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein.
Extra-mitochondrial prosurvival BCL-2 (show BCL2 Proteins) proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.
Missense mutation in SUFU gene is associated with Joubert Syndrome with Cranio-facial and Skeletal Defects.
In conclusion, this study showed the potential of miR (show MLXIP Proteins)-342-3p as a therapeutic target to promote bone regeneration by modulating expression of Sufu in UCMSCs.
miRNA-194 is oncogenic and promotes gastric cancer cell proliferation and migration by activating Wnt (show WNT2 Proteins) signaling, at least in part, via suppression of SUFU.
SUFU's role in Hedgehog (show SHH Proteins) signaling, tumor progression, and highlight a way in which BCCs can arise
In summary, these findings reveal Fbxl17 (show FBXL17 Proteins) as a novel regulator of the Hedgehog (show SHH Proteins) signaling pathway and highlight the perturbation of the Fbxl17 (show FBXL17 Proteins)-Sufu axis in the pathogenesis of medulloblastoma.
Through regulation of su(fu), miR (show MYLIP Proteins)-214 enables precise specification of muscle cell types by sharpening cellular responses to Hedgehog (show SHH Proteins).
beta-Arrestin2 (show ARRB2 Proteins) increases the Itch-mediated ubiquitylation of SuFu.
tissue development is differentially affected in response to the reduced SUFU levels.
Suppressor of Fused restraint of Hedgehog (show SHH Proteins) activity level is critical for osteogenic proliferation and differentiation during calvarial bone development
Sufu is upregulated in active Shh (show SHH Proteins) responding tissues and accompanies Gli (show GLI1 Proteins) activators translocating into and Gli (show GLI1 Proteins) repressors out of the nucleus.
Sufu deletion early in embryogenesis resulted in unstable Gli2 and Gli3 (show GLI3 Proteins) activity, leading to the ectopic activation of Shh (show SHH Proteins) signaling.
Thus, we provide evidence that Sufu is involved in the genetic network that restricts the posterior expression of Gli2/3/Hand2 (show HAND2 Proteins) and Gremlin (show GREM1 Proteins)/Fgf in limb bud patterning.
Results showed that the Thr396 residue of Sufu is specifically required for regulation of Gli3 (show GLI3 Proteins) but not Gli2 implying a novel Sufu-mediated mechanism in which Gli2 activator and Gli3 (show GLI3 Proteins) repressor are differentially regulated.
findings demonstrate that perturbations of Sufu and Kif7 affect Gli (show GLI1 Proteins) activity and recapitulate the full spectrum of vertebrate limb defects, ranging from severe truncation to polydactyly.
Hh signaling results in reduced Sufu protein levels and Sufu dissociation from Gli (show GLI1 Proteins) proteins in the nucleus, highlighting critical functions of Sufu in the nucleus.
The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.
, suppressor of fused
, suppressor of fused homolog