TY  - JOUR
AU  - Popović, Natasa M
AU  - Ruždijić, Sabera
AU  - Kanazir, Dusan T.
AU  - Niciforović, Ana
AU  - Adžić, Miroslav
AU  - Paraskevopoulou, Elissavet
AU  - Pantelidou, Constantia
AU  - Radojcić, Marija B
AU  - Demonacos, Constantinos
AU  - Krstić-Demonacos, Marija
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1375
AB  - The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
T2  - Steroids
T1  - Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae
IS  - 6
VL  - 75
EP  - 465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1375
ER  - 

@article{
author = "Popović, Natasa M and Ruždijić, Sabera and Kanazir, Dusan T. and Niciforović, Ana and Adžić, Miroslav and Paraskevopoulou, Elissavet and Pantelidou, Constantia and Radojcić, Marija B and Demonacos, Constantinos and Krstić-Demonacos, Marija",
year = "2010",
abstract = "The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.",
journal = "Steroids",
title = "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae",
number = "6",
volume = "75",
pages = "465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1375"
}

Popović, N. M., Ruždijić, S., Kanazir, D. T., Niciforović, A., Adžić, M., Paraskevopoulou, E., Pantelidou, C., Radojcić, M. B., Demonacos, C.,& Krstić-Demonacos, M.. (2010). Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids, 75(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1375

Popović NM, Ruždijić S, Kanazir DT, Niciforović A, Adžić M, Paraskevopoulou E, Pantelidou C, Radojcić MB, Demonacos C, Krstić-Demonacos M. Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids. 2010;75(6):null-465.
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

Popović, Natasa M, Ruždijić, Sabera, Kanazir, Dusan T., Niciforović, Ana, Adžić, Miroslav, Paraskevopoulou, Elissavet, Pantelidou, Constantia, Radojcić, Marija B, Demonacos, Constantinos, Krstić-Demonacos, Marija, "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae" in Steroids, 75, no. 6 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Niciforović, Ana
AU  - Vucić, Vesna
AU  - Nešković-Konstantinović, Zora B.
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Radojcić, Marija B
AU  - Spasić, Mihajlo
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1655
AB  - There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.
T2  - Redox Report
T1  - Systemic NF-kappa B activation in blood cells of breast cancer patients
IS  - 1
VL  - 11
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1655
ER  - 

@article{
author = "Adžić, Miroslav and Niciforović, Ana and Vucić, Vesna and Nešković-Konstantinović, Zora B. and Spasić, Snezana D and Jones, David R and Radojcić, Marija B and Spasić, Mihajlo",
year = "2006",
abstract = "There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.",
journal = "Redox Report",
title = "Systemic NF-kappa B activation in blood cells of breast cancer patients",
number = "1",
volume = "11",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1655"
}

Adžić, M., Niciforović, A., Vucić, V., Nešković-Konstantinović, Z. B., Spasić, S. D., Jones, D. R., Radojcić, M. B.,& Spasić, M.. (2006). Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report, 11(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1655

Adžić M, Niciforović A, Vucić V, Nešković-Konstantinović ZB, Spasić SD, Jones DR, Radojcić MB, Spasić M. Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report. 2006;11(1):null-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

Adžić, Miroslav, Niciforović, Ana, Vucić, Vesna, Nešković-Konstantinović, Zora B., Spasić, Snezana D, Jones, David R, Radojcić, Marija B, Spasić, Mihajlo, "Systemic NF-kappa B activation in blood cells of breast cancer patients" in Redox Report, 11, no. 1 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .