The Regulation of Activity of Main Mevalonic Acid Pathway Enzymes: Farnesyl Diphosphate Synthase, 3-Hydroxy-3-methylglutaryl-CoA Reductase, and Squalene Synthase in Yeast Saccharomyces cerevisiae

2000 ◽  
Vol 267 (1) ◽  
pp. 473-477 ◽  
Author(s):  
Anna Szkopińska ◽  
Ewa Świeżewska ◽  
Francis Karst
2005 ◽  
Vol 52 (1) ◽  
pp. 221-232 ◽  
Author(s):  
Kariona Grabińska ◽  
Grazyna Sosińska ◽  
Jacek Orłowski ◽  
Ewa Swiezewska ◽  
Thierry Berges ◽  
...  

In the yeast Saccharomyces cerevisiae the RER2 and SRT1 genes encode Rer2 and Srt1 proteins with cis-prenyltransferase (cis-PT-ase) activity. Both cis-PT-ases utilize farnesyl diphosphate (FPP) as a starter for polyprenyl diphosphate (dolichol backbone) formation. The products of the Rer2 and Srt1 proteins consist of 14-17 and 18-23 isoprene units, respectively. In this work we demonstrate that deletion or overexpression of SRT1 up-regulates the activity of Rer2p and dolichol content. However, upon overexpression of SRT1, preferential synthesis of longer-chain dolichols and a decrease in the amount of the shorter species are observed. Furthermore, overexpression of the ERG20 gene (encoding farnesyl diphosphate synthase, Erg20p) induces transcription of SRT1 mRNA and increases the levels of mRNA for RER2 and DPM1 (dolichyl phosphate mannose synthase, Dpm1p). Subsequently the enzymatic activity of Rer2p and dolichol content are also increased. However, the amount of Dpm1p or its enzymatic activity remain unchanged.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1437
Author(s):  
Fauziah Mohd Jaafar ◽  
Baptiste Monsion ◽  
Mourad Belhouchet ◽  
Peter P. C. Mertens ◽  
Houssam Attoui

Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, Hepacivirus), dengue virus (Flavivirus), African swine fever virus (Asfarviridae) and poliovirus (Picornaviridae). We assess the antiviral effect of fluvastatin in cells infected with orbiviruses (bluetongue virus (BTV) and Great Island virus (GIV)). The synthesis of orbivirus outer-capsid protein VP2 (detected by confocal immunofluorescence imaging) was used to assess levels of virus replication, showing a reduction in fluvastatin-treated cells. A reduction in virus titres of ~1.7 log (98%) in fluvastatin-treated cells was detected by a plaque assay. We have previously identified a fourth non-structural protein (NS4) of BTV and GIV, showing that it interacts with lipid droplets in infected cells. Fluvastatin, which inhibits 3-hydroxy 3-methyl glutaryl CoA reductase in the mevalonic acid pathway, disrupts these NS4 interactions. These findings highlight the role of the lipid pathways in orbivirus replication and suggest a greater role for the membrane-enveloped orbivirus particles than previously recognised. Chemical intermediates of the mevalonic acid pathway were used to assess their potential to rescue orbivirus replication. Pre-treatment of IFNAR(−/−) mice with fluvastatin promoted their survival upon challenge with live BTV, although only limited protection was observed.


2013 ◽  
Vol 13 (1) ◽  
pp. 68 ◽  
Author(s):  
Agata Maciejak ◽  
Agata Leszczynska ◽  
Ilona Warchol ◽  
Monika Gora ◽  
Joanna Kaminska ◽  
...  

2015 ◽  
Vol 6 (1) ◽  
pp. 17-33 ◽  
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Tarik A. Mohamed ◽  
Abdelsamed I. ElShamy ◽  
Abou-El-Hamd H. Mohamed ◽  
Usama A. Mahalel ◽  
...  

2017 ◽  
Vol 17 (4) ◽  
Author(s):  
Sebastián Rubat ◽  
Ignacio Varas ◽  
Romina Sepúlveda ◽  
Daniel Almonacid ◽  
Fernando González-Nilo ◽  
...  

2008 ◽  
Vol 148 (3) ◽  
pp. 1219-1228 ◽  
Author(s):  
Maya Sapir-Mir ◽  
Anahit Mett ◽  
Eduard Belausov ◽  
Shira Tal-Meshulam ◽  
Ahuva Frydman ◽  
...  

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