PCSK9-mediated LDL receptor degradation (Homo sapiens)

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1EndocytosisHepatocyteGolgi apparatusLDL cholesterolLDLRPCSK9PCSK9LDLRLDLRLDL-receptor synthesisLDLRPCSK9LDLRLysosomaldegradationPCSK9LDLRPCSK9LDLRPCSK9SecretionLDL-receptor recyclingLDLREndosomeLDLRLDLR


Description

Exogenously, circulating PCSK9 (Proprotein convertase subtilisin/kexin type 9) protein binds to LDLR (LDL receptor). Once internalized into the liver cell, the PCSK9 protein directs the LDLR to the lysosome for degradation. Intrinsically, PCSK9, which is secreted from the Golgi apparatus, binds the LDLR before it reaches the cell surface, leading it to lysosomal degradation. However, the precise mechanisms by which the intrinsic degradation pathway operates are still unknown. Abbreviations: LDLR, LDL receptor; PCSK9, proprotein convertase subtilisin/kexin type 9.

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Bibliography

  1. Brautbar A, Ballantyne CM; ''Pharmacological strategies for lowering LDL cholesterol: statins and beyond.''; Nat Rev Cardiol, 2011 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128066view00:05, 24 January 2024EweitzA bit more mitigation of Golgi distortion in website
128065view00:04, 24 January 2024EweitzTry further mitigating Golgi distortion in website rendering
128064view00:03, 24 January 2024EweitzMitigate Golgi distortion (site shows it partly extracellular, PathVisio shows it fully intracellular); upgrade "LDL particles" label to "LDL cholesterol" metabolite node
128063view23:55, 23 January 2024EweitzOntology Term : 'cholesterol metabolic pathway' added !
128062view23:52, 23 January 2024EweitzOntology Term : 'hepatocyte' added !
116729view10:27, 11 May 2021EweitzModified title
89409view20:16, 10 September 2016AlexanderPicoModified title
89108view15:11, 22 August 2016EveloModified description
89107view15:10, 22 August 2016EveloModified title
89106view15:10, 22 August 2016EveloModified title
89105view15:09, 22 August 2016EveloModified description
88292view15:00, 1 August 2016FehrhartOntology Term : 'lipoprotein metabolic pathway' added !
83009view09:34, 17 November 2015FehrhartUpdated ensembl ID for LDLR
78515view10:29, 7 January 2015MaintBotadded missing graphIds
77448view13:36, 9 September 2014SusanConnect line
77430view11:51, 8 September 2014SusanModified description
77429view11:50, 8 September 2014SusanNew pathway

External references

DataNodes

NameTypeDatabase referenceComment
LDL cholesterolMetabolite47774 (ChEBI)
LDLRGeneProductENSG00000130164 (Ensembl)
PCSK9GeneProductENSG00000169174 (Ensembl)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2846"
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