The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion

Deng, Shijun; Shen, Yishi; Gu, Hongmei; Guo, Shoudong; Wu, Shan-Rong; Zhang, Da Wei

doi:10.1016/j.bbalip.2020.158660

Cited by 21 publications

(26 citation statements)

References 50 publications

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“…12,13 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a glycoprotein consisting of 692 amino acids belonging to the family of proprotein converters. 14 It is a type of serine protease, which was discovered as a regulated protein after apoptosis induction in primary cerebellar neurons. Therefore, it is known as neural apoptosis-regulated convertase 1.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects

Erol

Oğuz

Anuk

et al. 2021

Congenital Anomalies

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It was aimed to evaluate the levels of maternal serum proprotein convertase subtilisin/ kexin type 9 (PCSK9) in pregnant women with a fetus diagnosed with open neural tube defects (NTDs). This case-control study included 38 pregnant women carrying fetuses with open NTDs and 44 age-matched, pregnant women with no specified risk factors.Comparisons were made of the groups in respect of demographic and clinical data and PCSK9 levels. To examine the performance of PCSK9 levels in the prediction of fetal open NTDs, receiver operating characteristic (ROC) curve analysis was used. In the first and second trimesters, PCSK9 levels were determined to be lower in the NTD group than in the control group (p = 0.010 and p = 0.015, respectively). In the first trimester, the lower PCSK9 levels in the NTD group were not statistically significant (p = 0.575). In the second trimester, the ROC curve value with the best balance of sensitivity/specificity for PCSK9 was 71.9 ng/ml (84.6% sensitivity, 51.7% specificity) and in the first and second trimester combined, 74.4 ng/ml (81.6% sensitivity, 45.5% specificity) (p = 0.015, p = 0.036, respectively). PCSK9 may be involved in the etiopathogenesis of open NTDs at the critical steps of fetal neuronal differentiation. Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs.

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Section: Introductionmentioning

confidence: 99%

A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects

Erol

Oğuz

Anuk

et al. 2021

Congenital Anomalies

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“…21 In this context, the C-terminal domain of PCSK9 might interact with a potential cargo receptor to mediate PCSK9 secretion, with SEC24A, SEC24B, and SEC24C, but not SEC24D, involved in endogenous secretion. 22 This suggests a receptor-mediated mechanism for the recruitment of PCSK9 into coat protein II vesicles. The cargo receptor sorts soluble proteins into the coat protein II complex.…”

Section: The Biologymentioning

confidence: 96%

Proprotein Convertase Subtilisin/Kexin Type 9

Macchi

Ferri

Sirtori

et al. 2021

The American Journal of Pathology

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“…The CTD is positively charged and may interact with the negatively charged ligand-binding repeats of LDLR in the acidic endosomal environment, blocking recycling of the receptor (14,15). In addition, partial deletion of the CTD markedly damages PCSK9 secretion, indicating its essential role in this process (16,17). However, the underlying mechanism is unclear.…”

Section: Pcsk9 Functionmentioning

confidence: 99%

“…However, the underlying mechanism is unclear. Our recent study suggests that the CTD mediates PCSK9 secretion, possibly via a coat protein complex II (COPII) component Sec24 (17).…”

Section: Pcsk9 Functionmentioning

confidence: 99%

Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications

Xia

Peng

et al. 2021

Front. Cardiovasc. Med.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptor (LDLR) and plays a central role in regulating plasma levels of LDL cholesterol levels, lipoprotein(a) and triglyceride-rich lipoproteins, increasing the risk of cardiovascular disease. Additionally, PCSK9 promotes degradation of major histocompatibility protein class I and reduces intratumoral infiltration of cytotoxic T cells. Inhibition of PCSK9 increases expression of LDLR, thereby reducing plasma levels of lipoproteins and the risk of cardiovascular disease. PCSK9 inhibition also increases cell surface levels of major histocompatibility protein class I in cancer cells and suppresses tumor growth. Therefore, PCSK9 plays a vital role in the pathogenesis of cardiovascular disease and cancer, the top two causes of morbidity and mortality worldwide. Monoclonal anti-PCSK9 antibody-based therapy is currently the only available treatment that can effectively reduce plasma LDL-C levels and suppress tumor growth. However, high expenses limit their widespread use. PCSK9 promotes lysosomal degradation of its substrates, but the detailed molecular mechanism by which PCSK9 promotes degradation of its substrates is not completely understood, impeding the development of more cost-effective alternative strategies to inhibit PCSK9. Here, we review our current understanding of PCSK9 and focus on the regulation of its expression and functions.

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The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion

Cited by 21 publications

References 50 publications

A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects

A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects

Proprotein Convertase Subtilisin/Kexin Type 9

Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications

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