FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2592012303> ?p ?o ?g. }

• W2592012303 endingPage "6189" @default.
• W2592012303 startingPage "6177" @default.
• W2592012303 abstract "The lysosomal acid β-glucosidase GBA1 and the non-lysosomal β-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feedback loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of β-glucosidase activity in general. The lysosomal acid β-glucosidase GBA1 and the non-lysosomal β-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feedback loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of β-glucosidase activity in general." @default.
• W2592012303 created "2017-03-16" @default.
• W2592012303 creator A5007309669 @default.
• W2592012303 creator A5011998711 @default.
• W2592012303 creator A5017198064 @default.
• W2592012303 creator A5018451838 @default.
• W2592012303 creator A5021535678 @default.
• W2592012303 creator A5022096672 @default.
• W2592012303 creator A5030131769 @default.
• W2592012303 creator A5031636056 @default.
• W2592012303 creator A5041979288 @default.
• W2592012303 creator A5043062485 @default.
• W2592012303 creator A5049097173 @default.
• W2592012303 creator A5071331160 @default.
• W2592012303 creator A5076980316 @default.
• W2592012303 creator A5077869340 @default.
• W2592012303 creator A5084617813 @default.
• W2592012303 creator A5084823117 @default.
• W2592012303 creator A5088432021 @default.
• W2592012303 date "2017-04-01" @default.
• W2592012303 modified "2023-10-16" @default.
• W2592012303 title "Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease" @default.
• W2592012303 cites W1481879356 @default.
• W2592012303 cites W1911261579 @default.
• W2592012303 cites W1965046438 @default.
• W2592012303 cites W1972455024 @default.
• W2592012303 cites W1986341243 @default.
• W2592012303 cites W1993796718 @default.
• W2592012303 cites W1994020466 @default.
• W2592012303 cites W2005658789 @default.
• W2592012303 cites W2007348345 @default.
• W2592012303 cites W2013222950 @default.
• W2592012303 cites W2017711362 @default.
• W2592012303 cites W2022770236 @default.
• W2592012303 cites W2023161091 @default.
• W2592012303 cites W2028245787 @default.
• W2592012303 cites W2041175508 @default.
• W2592012303 cites W2055445325 @default.
• W2592012303 cites W2056402458 @default.
• W2592012303 cites W2068015921 @default.
• W2592012303 cites W2071309923 @default.
• W2592012303 cites W2080952606 @default.
• W2592012303 cites W2089184179 @default.
• W2592012303 cites W2090243158 @default.
• W2592012303 cites W2106528949 @default.
• W2592012303 cites W2124663723 @default.
• W2592012303 cites W2130588606 @default.
• W2592012303 cites W2151754172 @default.
• W2592012303 cites W2153518194 @default.
• W2592012303 cites W2161571120 @default.
• W2592012303 cites W2163635263 @default.
• W2592012303 cites W2167876561 @default.
• W2592012303 cites W2171954574 @default.
• W2592012303 cites W2183090606 @default.
• W2592012303 cites W2206291032 @default.
• W2592012303 cites W2257876259 @default.
• W2592012303 cites W2472092927 @default.
• W2592012303 doi "https://doi.org/10.1074/jbc.m116.762831" @default.
• W2592012303 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5391749" @default.
• W2592012303 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28258214" @default.
• W2592012303 hasPublicationYear "2017" @default.
• W2592012303 type Work @default.
• W2592012303 sameAs 2592012303 @default.
• W2592012303 citedByCount "19" @default.
• W2592012303 countsByYear W25920123032017 @default.
• W2592012303 countsByYear W25920123032018 @default.
• W2592012303 countsByYear W25920123032019 @default.
• W2592012303 countsByYear W25920123032020 @default.
• W2592012303 countsByYear W25920123032021 @default.
• W2592012303 countsByYear W25920123032022 @default.
• W2592012303 crossrefType "journal-article" @default.
• W2592012303 hasAuthorship W2592012303A5007309669 @default.
• W2592012303 hasAuthorship W2592012303A5011998711 @default.
• W2592012303 hasAuthorship W2592012303A5017198064 @default.
• W2592012303 hasAuthorship W2592012303A5018451838 @default.
• W2592012303 hasAuthorship W2592012303A5021535678 @default.
• W2592012303 hasAuthorship W2592012303A5022096672 @default.
• W2592012303 hasAuthorship W2592012303A5030131769 @default.
• W2592012303 hasAuthorship W2592012303A5031636056 @default.
• W2592012303 hasAuthorship W2592012303A5041979288 @default.
• W2592012303 hasAuthorship W2592012303A5043062485 @default.
• W2592012303 hasAuthorship W2592012303A5049097173 @default.
• W2592012303 hasAuthorship W2592012303A5071331160 @default.
• W2592012303 hasAuthorship W2592012303A5076980316 @default.
• W2592012303 hasAuthorship W2592012303A5077869340 @default.
• W2592012303 hasAuthorship W2592012303A5084617813 @default.
• W2592012303 hasAuthorship W2592012303A5084823117 @default.
• W2592012303 hasAuthorship W2592012303A5088432021 @default.
• W2592012303 hasBestOaLocation W25920123031 @default.
• W2592012303 hasConcept C104317684 @default.
• W2592012303 hasConcept C170493617 @default.
• W2592012303 hasConcept C181199279 @default.
• W2592012303 hasConcept C185592680 @default.
• W2592012303 hasConcept C190283241 @default.
• W2592012303 hasConcept C2777851122 @default.
• W2592012303 hasConcept C2778264360 @default.
• W2592012303 hasConcept C2778703144 @default.
• W2592012303 hasConcept C2779994418 @default.

• next