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Two novel variants in the PSAP gene were identified in a patient with metachromatic leukodystrophy.
Saposin C or its precursor (PSAP) function as an androgen-agonist and upregulate androgen receptor and prostate-specific antigen expression/activity in androgen-responsive prostate cancer cells LNCaP, TRAMP-C1 and -C2, and CWR 22RV1.
Prosaposin is an androgen-target gene and its expression in androgen-responsive prostate cancer cells can be upregulated by male hormones.
The prosaposin gene is amplified in human metastatic AI PCa cell lines and punch biopsy samples of prostate cancer xenografts and lymph node metastases.
The findings of this study suggest that PSAP can promote glioma cell proliferation via the TLR4/NF-kappaB signaling pathway and may be an important target for glioma treatment.
Accumulating evidence suggests that PGRN is essential for proper lysosomal function, but the precise mechanisms involved are not known. Here, we show that PGRN facilitates neuronal uptake and lysosomal delivery of prosaposin (PSAP), the precursor of saposin peptides that are essential for lysosomal glycosphingolipid degradation.
Both PSAP reduction and overexpression lead to significantly elevated extracellular progranulin (PGRN) levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction.
Study demonstrated that the binding of CST3 and PSAP decreased the inhibitory effects of CST3 on proteinase in vitro. The co-localization of both proteins was detected in cultured cells and in Bunina body-containing motor neurons from patients with amyotrophic lateral sclerosis, suggesting that they might be involved in the process of Bunina body formation.
This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement.
an extensive review of all the PSAP-causative variants published in the literature to date, accounting for a total of 10 PSAP allele types (review)
Our findings suggest a novel pharmacological approach to Sap C deficiency directed to treat major secondary pathological aspects in this disorder.
PSAP is a secreted biomarker.
Data suggested that the abundance of Psap in sperm sample may be a sensitive endpoint to predict PCB exposure.
Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin.
findings support a lung metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP in breast cancer
Mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models.
Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H.
Saposin C protects glucocerebrosidase against alpha-synuclein inhibition.
Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and prosaposin fragment or saposin B.
These findings suggested that prosaposin might enhance estrogen receptor alpha-mediated signaling axis and play a role in breast cancer development and progression.
Data show that matrix (ECM) stiffness leads to mechano-signal transduction in mesenchymal stem cells (MSC), which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin.
This study demonistrated that Spiral ganglion degeneration and hearing loss as a consequence of satellite cell death in saposin B-deficient mice.
Low levels of prosaposin and its receptors in the mouse brain suggest the participation of prosaponin in pathological changes in the brains of dystrophic mdx mice.
These data show functional association between GPR37, prosaposin, and GM1 ganglioside in the plasma membrane.
The saposin A and saposin B deficiency AB(-/-) mice develop accumulation of multiple glycosphingolipids in various organs.
Prosaposin is involved in the regulation of muscle differentiation of regenerated fibres
Saposins A and B deficiencies attenuated GalCer-beta-galactosylceramidase and GM1-beta-galactosidase functions in the degradation of lactosylceramide in the liver.
These data suggest that prosaposin plays an important role in the neuronal maturation processes of the vestibular sensory epithelium and the maintenance of normal vestibular system function.
The saposin C deficient mice backcrossed to point mutated GCase mimics the central nervous system phenotype and biochemistry of some type 3 (neuronopathic) variants of Gaucher disease.
These results suggest the in vivo role of saposin C in axonal membrane homeostasis, the disruption of which leads to neurodegeneration in lysosomal storage disease.
UGT1 aids in the folding of sequential domain-containing proteins such as prosaposin.
Saposin C has multiple roles in glycosphingolipid catabolism and functions in Central Nervous System independent of its role as an stabilizer of GCase.
Immunoblot studies indicated that prosaposin, already abundant in the brain of WT, was dramatically increased in Sap-D(-/-)
A saposin-like motif within the first half of the prosaposin C terminus contains the sortilin recognition site.
The growth promotion and anti-apoptotic activity of prosaposin is partly through the PI3K/Akt signal pathway.
reconstruction of the order of internal duplications that gave rise to the four saposins by using phylogenetic tools
identified 68 single-nucleotide polymorphisms and 9 indels in the pig PASP gene, and three single-nucleotide polymorphisms were nonsynonymous substitutions
Saposin B (Sap B) is not a limiting factor of the coupled Sap B-arylsulfatase A reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels.
This gene encodes a highly conserved glycoprotein which is a precursor for 4 cleavage products: saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease, Tay-Sachs disease, and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants encoding different isoforms.
, sphingolipid activator protein-1
, snoRNA MBII-198
, sulfated glycoprotein 1
, prosaposin (sulfated glycoprotein, sphingolipid hydrolase activator)
, prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy)
, proactivator polypeptide-like