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Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2
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The gene expression of PCSK9 is negatively regulated by SREBPs.
“The gene expression of PCSK9 is negatively regulated by SREBPs, and PCSK9 protein is a key mediator for LDLR internalization and degradation by ubiquitination.”
From Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression (2021) · cites this paper as [34]
The section “Regulation of the promoter activity of PCSK9 by overexpression of SREBPs” reports that nuclear SREBPs dramatically increased PCSK9 promoter transcription. The paper describes SREBP-1 and SREBP-2 as activators of PCSK9 expression, contrary to the claimed negative regulation. (LLM, conf=0.94)
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Experimental — accuracy not yet measuredPCSK9 protein is a key mediator for LDLR degradation by ubiquitination.
“The PCSK9 protein is a key mediator for LDLR degradation by ubiquitination, and its inhibitors have been applied to clinical trials for hypocholesterolemia (33, 34).”
From Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression (2021) · cites this paper as [34]
The Abstract says PCSK9 promotes LDLR internalization and degradation, and describes prevention of LDLR recycling or targeting it for lysosomal degradation. Neither that passage nor the Discussion identifies ubiquitination as the mechanism, so the mechanistic part of the claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLDLR and PCSK9 are downstream genes of SREBPs.
“LDLR and PCSK9 are downstream genes of SREBPs.”
From Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression (2021) · cites this paper as [34]
The promoter of the PCSK9 gene contains a serum response element (SRE) that makes its transcription subject to regulation by SREBP-2.
“The promoter of PCSK9 gene contains a serum response element (SRE) that makes its transcription subject to regulation by SREBP-231.”
From Triciribine increases LDLR expression and LDL uptake through stabilization of LDLR mRNA (2018) · cites this paper as [31]
PCSK9 is an SREBP2 target.
“PCSK9 is an SREBP2 target (30,31)”
From A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes (2016) · cites this paper as [30]
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Citations
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Norata, G. D., Tibolla, G., & Catapano, A. L. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-140025 · Cited by 127
Expanding biology of PCSK9: roles in atherosclerosis and beyond
Seidah, N. G., & Garçon, D. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01057-z · Cited by 76
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Loregger, A., Cook, E. C. L., Nelson, J. K., Moeton, M., Sharpe, L. J., Engberg, S., Karimova, M., Lambert, G., Brown, A. J., & Zelcer, N. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00890-15 · Cited by 48
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Triciribine increases LDLR expression and LDL uptake through stabilization of LDLR mRNA
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Metadata
- Authors
- Jeong, H. J., Lee, H.-S., Kim, K.-S., Kim, Y.-K., Yoon, D., & Park, S. W.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 49
- Issue
- 2
- Pages
- 399-409
- ISSN
- 0022-2275
- Cited by
- 331
- References
- 3
- Language
- en
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