Protein Kinase D Negatively Regulates Hepatitis C Virus Secretion through Phosphorylation of Oxysterol-binding Protein and Ceramide Transfer Protein

Amako, Yutaka; Syed, Gulam Hussain; Siddiqui, Aleem

doi:10.1074/jbc.m110.182097

Cited by 83 publications

(80 citation statements)

References 61 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings suggest that HCV tightly regulates the conventional Golgi-secretory pathway and musters the available resources to facilitate selective secretion of the HCV virion. Indeed, we observed that the overall secretion of secretory proteins was hindered in HCV-infected cells (35). A recent addition to the list of PI4P binding proteins is GOLPH3, a Golgi protein that requires PI4P for its Golgi localization through direct binding via a novel domain unrelated to pleckstrin-homology domains (37).…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 91%

“…Immunofluorescence-Infected and/or transfected cells grown on glass coverslips were prepared as described previously (34,35). The slides were analyzed by confocal laser scanning microscopy (Olypmus FV1000).…”

Section: Methodsmentioning

confidence: 99%

“…10 g of extracted HCV RNA was used for electroporation using a Gene Pulser Xcell electroporation system as described previously (Bio-Rad) (34,35).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that OSBP plays a key role in HCV secretion and that the HCV non-structural protein 5A (NS5A) interacts with OSBP to facilitate this process (34). We have also shown that protein kinase D (PKD), a central modulator of Golgi trafficking, negatively regulates HCV secretion through phosphorylation-mediated inhibition of OSBP and CERT function and that HCV inhibits PKD activation (35). Intriguingly, PKD is known to activate PI4KIII␤ at the TGN (36).…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

See 3 more Smart Citations

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

Bishé

Syed

Field

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background:The secretory mechanism of hepatitis C virus (HCV) is currently unknown. Results: Depletion of the Golgi PI4P levels or PI4P-binding protein GOLPH3 reduces HCV secretion and leads to accumulation of intracellular virions. Conclusion: PI4P and binding proteins implicate the Golgi as a necessary component of HCV secretion. Significance: Characterization of the components of the HCV secretion pathway could lead to new therapeutic targets.

show abstract

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

“…10 g of extracted HCV RNA was used for electroporation using a Gene Pulser Xcell electroporation system as described previously (Bio-Rad) (34,35).…”

Section: Methodsmentioning

confidence: 99%

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

See 2 more Smart Citations

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

Bishé

Syed

Field

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The interaction between the oxysterol binding protein (OSBP) and the viral non‐structural protein NS5A promotes HCV secretion. Accordingly, inhibition of OSBP phosphorylation influenced negatively HCV maturation and secretion 51, 52.…”

Section: Hcv Interaction With Lipid and Lipoprotein Metabolismmentioning

confidence: 99%

Hepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism

Pirro

Bianconi

Francisci

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

From viral binding to the hepatocyte surface to extracellular virion release, the replication cycle of the hepatitis C virus (HCV) intersects at various levels with lipid metabolism; this leads to a derangement of the lipid profile and to increased viral infectivity. Accumulating evidence supports the crucial regulatory role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism. Notably, a complex interaction between HCV and PCSK9 has been documented. Indeed, either increased or reduced circulating PCSK9 levels have been observed in HCV patients; this discrepancy might be related to several confounders, including HCV genotype, human immunodeficiency virus (HIV) coinfection and the ambiguous HCV‐mediated influence on PCSK9 transcription factors. On the other hand, PCSK9 may itself influence HCV infectivity, inasmuch as the expression of different hepatocyte surface entry proteins and receptors is regulated by PCSK9. The aim of this review is to summarize the current evidence about the complex interaction between HCV and liver lipoprotein metabolism, with a specific focus on PCSK9. The underlying assumption of this review is that the interconnections between HCV and PCSK9 may be central to explain viral infectivity.

show abstract

Structure, functions and regulation of CERT, a lipid‐transfer protein for the delivery of ceramide at the ER–Golgi membrane contact sites

Kumagai

Hanada

2019

FEBS Letters

View full text Add to dashboard Cite

The inter‐organelle transport of lipids must be regulated to ensure appropriate lipid composition of each organelle. In mammalian cells, ceramide synthesised in the endoplasmic reticulum (ER) is transported to the trans‐Golgi regions, where ceramide is converted to sphingomyelin (SM) with the concomitant production of diacylglycerol. Ceramide transport protein (CERT) transports ceramide from the ER to the trans‐Golgi regions at the ER–Golgi membrane contact sites (MCS). The function of CERT is down‐regulated by multisite phosphorylation of a serine‐repeat motif (SRM) and up‐regulated by phosphorylation of serine 315 in CERT. Multisite phosphorylation of the SRM is primed by protein kinase D, which is activated by diacylglycerol. The function of CERT is regulated by a phosphorylation‐dependent feedback mechanism in response to cellular requirements of SM. CERT‐dependent ceramide transport is also affected by the pool of phosphatidylinositol (PtdIns)‐4‐phosphate (PtdIns(4)P) in the trans‐Golgi regions, while the PtdIns(4)P pool is regulated by PtdIns‐4‐kinases and oxysterol‐binding protein. The ER‐Golgi MCS may serve as inter‐organelle communication zones, in which many factors work in concert to serve as an extensive rheostat of SM, diacylglycerol, cholesterol and PtdIns(4)P.

show abstract

Protein Kinase D Negatively Regulates Hepatitis C Virus Secretion through Phosphorylation of Oxysterol-binding Protein and Ceramide Transfer Protein

Cited by 83 publications

References 61 publications

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

Hepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism

Structure, functions and regulation of CERT, a lipid‐transfer protein for the delivery of ceramide at the ER–Golgi membrane contact sites

Contact Info

Product

Resources

About