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Hem12, an enzyme of heme biosynthesis pathway, is monoubiquitinated by Rsp5 ubiquitin ligase in yeast cells

100%

Chelstowska A., Jastrzebska Z., Kaminska J., Sadurska A., Plochocka D., Rytka J., Zoladek T.

2015

vol. 62

issue 3

509-515

Heme biosynthesis pathway is conserved in yeast and humans and hem12 yeast mutants mimic porphyria cutanea tarda (PCT), a hereditary human disease caused by mutations in the UROD gene. Even though mutations in other genes also affect UROD activity and predispose to sporadic PCT, the regulation of UROD is unknown. Here, we used yeast as a model to study regulation of Hem12 by ubiquitination and involvement of Rsp5 ubiquitin ligase in this process. We found that Hem12 is monoubiquitinated in vivo by Rsp5. Hem12 contains three conserved lysine residues located on the protein surface that can potentially be ubiquitinated and lysine K8 is close to the 36-LPEY-39 (PY) motif which binds WW domains of the Rsp5 ligase. The hem12-K8A mutation results in a defect in cell growth on a glycerol medium at 38°C but it does not affect the level of Hem12. The hem12-L36A,P37A mutations which destroy the PY motif result in a more profound growth defect on both, glycerol and glucose-containing media. However, after several passages on the glucose medium, the hem12-L36A,P37A cells adapt to the growth medium owing to higher expression of hem12-L36A,P37A gene and higher stability of the mutant Hem12-L36A,P37A protein. The Hem12 protein is downregulated upon heat stress in a Rsp5-independent way. Thus, Rsp5-dependent Hem12 monoubiquitination is important for its functioning, but not required for its degradation. Since Rsp5 has homologs among the Nedd4 family of ubiquitin ligases in humans, a similar regulation by ubiquitination might be also important for functioning of the human UROD.

Molecular analysis of three novel G6PD variants: G6PD Pedoplis-Ckaro, G6PD Piotrkow and G6PD Krakow

84%

Maciag M., Plochocka D., Jablonska-Skwiecinska E., Mendek-Czajkowska E., Golaszewska E., Strojny W., Balwierz W., Zdebska E., Burzynska B.

2007

vol. 54

issue 4

877-881

We present three novel mutations in the G6PD gene and discuss the changes they cause in the 3-dimensional structure of the enzyme: 573C→G substitution that predicts Phe to Leu at position 191 in the C-terminus of helix αe, 851T→C mutation which results in the substitution 284Val→→Ala in the β+α domain close to the C-terminal part of helix αj, and 1175T→C substitution that predicts Ile to Thr change at position 392.

Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study

68%

Leszczynska A., Gora M., Plochocka D., Hoser G., Szkopinska A., Koblowska M., Iwanicka-Nowicka R., Kotlinski M., Rawa K., Kiliszek M., Burzynska B.

2011

vol. 58

issue 4

635-639

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

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3 Acta Biochimica Polonica

1 2015

1 2011

1 2007

3 Plochocka D.

2 Burzynska B.

1 Balwierz W.

1 Chelstowska A.

1 Golaszewska E.

1 Gora M.

1 Hoser G.

1 Iwanicka-Nowicka R.

1 Jablonska-Skwiecinska E.

1 Jastrzebska Z.

1 Kaminska J.

1 Kiliszek M.

1 Koblowska M.

1 Kotlinski M.

1 Leszczynska A.

1 Maciag M.

1 Mendek-Czajkowska E.

1 Rawa K.

1 Rytka J.

1 Sadurska A.

1 Strojny W.

1 Szkopinska A.

1 Zdebska E.

1 Zoladek T.

Search results

Hem12, an enzyme of heme biosynthesis pathway, is monoubiquitinated by Rsp5 ubiquitin ligase in yeast cells

Molecular analysis of three novel G6PD variants: G6PD Pedoplis-Ckaro, G6PD Piotrkow and G6PD Krakow

Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study