TY  - JOUR
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša
AU  - Popović, Jelena
AU  - Krstić, A.
AU  - Milivojević, Milena
AU  - Stevanović, Milena
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/526
AB  - The SOX18 transcription factor plays an important role in endothelial cell specification, angiogenesis and atherogenesis. By profiling transcription factor interactions (TranSignal TM TF Protein Array) we identified several transcription factors implicated in angiogenesis that have the ability to bind to the SOX18 optimal promoter region in vitro. In this report we focused our attention on distinct transcription factors identified by the array as belonging to AP-1 and CREB/ATF protein families. In particular, we analyzed the effects of CREB, JunB, c-Jun and ATF3 on SOX18 gene expression. Functional analysis revealed that CREB acts as a repressor, while JunB, c-Jun and ATF3 act as activators of SOX18 promoter activity. Our findings indicate that a transcriptional network that includes CREB, JunB, c-Jun and ATF3 could be involved in angiogenesis-related transcriptional regulation of the SOX18 gene.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression
EP  - 525
IS  - 3
SP  - 517
VL  - 63
DO  - 10.2298/ABS1103517P
ER  - 

@article{
author = "Petrović, Isidora and Kovačević Grujičić, Nataša and Popović, Jelena and Krstić, A. and Milivojević, Milena and Stevanović, Milena",
year = "2011",
abstract = "The SOX18 transcription factor plays an important role in endothelial cell specification, angiogenesis and atherogenesis. By profiling transcription factor interactions (TranSignal TM TF Protein Array) we identified several transcription factors implicated in angiogenesis that have the ability to bind to the SOX18 optimal promoter region in vitro. In this report we focused our attention on distinct transcription factors identified by the array as belonging to AP-1 and CREB/ATF protein families. In particular, we analyzed the effects of CREB, JunB, c-Jun and ATF3 on SOX18 gene expression. Functional analysis revealed that CREB acts as a repressor, while JunB, c-Jun and ATF3 act as activators of SOX18 promoter activity. Our findings indicate that a transcriptional network that includes CREB, JunB, c-Jun and ATF3 could be involved in angiogenesis-related transcriptional regulation of the SOX18 gene.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression",
pages = "525-517",
number = "3",
volume = "63",
doi = "10.2298/ABS1103517P"
}

Petrović, I., Kovačević Grujičić, N., Popović, J., Krstić, A., Milivojević, M.,& Stevanović, M.. (2011). Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 63(3), 517-525.
https://doi.org/10.2298/ABS1103517P

Petrović I, Kovačević Grujičić N, Popović J, Krstić A, Milivojević M, Stevanović M. Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression. in Archives of Biological Sciences. 2011;63(3):517-525.
doi:10.2298/ABS1103517P .

Petrović, Isidora, Kovačević Grujičić, Nataša, Popović, Jelena, Krstić, A., Milivojević, Milena, Stevanović, Milena, "Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression" in Archives of Biological Sciences, 63, no. 3 (2011):517-525,
https://doi.org/10.2298/ABS1103517P . .

TY  - JOUR
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/415
AB  - Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 by relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis.
PB  - Nature Publishing Group, New York
T2  - Experimental and Molecular Medicine
T1  - Early growth response protein 1 acts as an activator of SOX18 promoter
EP  - 142
IS  - 2
SP  - 132
VL  - 42
DO  - 10.3858/emm.2010.42.2.015
ER  - 

@article{
author = "Petrović, Isidora and Kovačević Grujičić, Nataša and Stevanović, Milena",
year = "2010",
abstract = "Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 by relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis.",
publisher = "Nature Publishing Group, New York",
journal = "Experimental and Molecular Medicine",
title = "Early growth response protein 1 acts as an activator of SOX18 promoter",
pages = "142-132",
number = "2",
volume = "42",
doi = "10.3858/emm.2010.42.2.015"
}

Petrović, I., Kovačević Grujičić, N.,& Stevanović, M.. (2010). Early growth response protein 1 acts as an activator of SOX18 promoter. in Experimental and Molecular Medicine
Nature Publishing Group, New York., 42(2), 132-142.
https://doi.org/10.3858/emm.2010.42.2.015

Petrović I, Kovačević Grujičić N, Stevanović M. Early growth response protein 1 acts as an activator of SOX18 promoter. in Experimental and Molecular Medicine. 2010;42(2):132-142.
doi:10.3858/emm.2010.42.2.015 .

Petrović, Isidora, Kovačević Grujičić, Nataša, Stevanović, Milena, "Early growth response protein 1 acts as an activator of SOX18 promoter" in Experimental and Molecular Medicine, 42, no. 2 (2010):132-142,
https://doi.org/10.3858/emm.2010.42.2.015 . .

TY  - JOUR
AU  - Petrović, Isidora
AU  - Nikčević, Gordana
AU  - Zarić, Jelena
AU  - Ruegg, Curzio
AU  - Stevanović, Milena
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/431
AB  - Angiogenesis, the process of generating new blood vessels, is essential to embryonic development, organ formation, tissue regeneration and remodeling, reproduction and wound healing. Also, it plays an important role in many pathological conditions, including chronic inflammation and cancer. Angiogenesis is regulated by a complex interplay of growth factors, inflammatory mediators, adhesion molecules, morphogens and guidance molecules. Transcription factor SOX18 is transiently expressed in nascent endothelial cells during embryonic development and postnatal angiogenesis, but little is known about signaling pathways controlling its expression. The aim of this study was to investigate whether pro-angiogenic molecules and pharmacological inhibitors of angiogenesis modulate SOX18 expression in endothelial cells. Therefore, we treated human umbilical vein endothelial cells (HUVEC) with angiogenic factors, extracellular matrix proteins, inflammatory cytokines and nonsteroidal anti-inflammatory drugs (NSAID) and monitored SOX18 expression. We have observed that the angiogenic factor VEGF and the inflammatory cytokine TNF increase, while the NSAID ibuprofen and NS398 decrease the SOX18 protein level. These results for the first time demonstrate that SOX18 expression is modulated by factors and drugs known to positively or negatively regulate angiogenesis. This opens the possibility of pharmacological manipulation of SOX18 gene expression in endothelial cells to stimulate or inhibit angiogenesis.
PB  - Versita, Warsaw
T2  - Central European Journal of Biology
T1  - VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC
EP  - 434
IS  - 4
SP  - 427
VL  - 5
DO  - 10.2478/s11535-010-0031-3
ER  - 

@article{
author = "Petrović, Isidora and Nikčević, Gordana and Zarić, Jelena and Ruegg, Curzio and Stevanović, Milena",
year = "2010",
abstract = "Angiogenesis, the process of generating new blood vessels, is essential to embryonic development, organ formation, tissue regeneration and remodeling, reproduction and wound healing. Also, it plays an important role in many pathological conditions, including chronic inflammation and cancer. Angiogenesis is regulated by a complex interplay of growth factors, inflammatory mediators, adhesion molecules, morphogens and guidance molecules. Transcription factor SOX18 is transiently expressed in nascent endothelial cells during embryonic development and postnatal angiogenesis, but little is known about signaling pathways controlling its expression. The aim of this study was to investigate whether pro-angiogenic molecules and pharmacological inhibitors of angiogenesis modulate SOX18 expression in endothelial cells. Therefore, we treated human umbilical vein endothelial cells (HUVEC) with angiogenic factors, extracellular matrix proteins, inflammatory cytokines and nonsteroidal anti-inflammatory drugs (NSAID) and monitored SOX18 expression. We have observed that the angiogenic factor VEGF and the inflammatory cytokine TNF increase, while the NSAID ibuprofen and NS398 decrease the SOX18 protein level. These results for the first time demonstrate that SOX18 expression is modulated by factors and drugs known to positively or negatively regulate angiogenesis. This opens the possibility of pharmacological manipulation of SOX18 gene expression in endothelial cells to stimulate or inhibit angiogenesis.",
publisher = "Versita, Warsaw",
journal = "Central European Journal of Biology",
title = "VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC",
pages = "434-427",
number = "4",
volume = "5",
doi = "10.2478/s11535-010-0031-3"
}

Petrović, I., Nikčević, G., Zarić, J., Ruegg, C.,& Stevanović, M.. (2010). VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC. in Central European Journal of Biology
Versita, Warsaw., 5(4), 427-434.
https://doi.org/10.2478/s11535-010-0031-3

Petrović I, Nikčević G, Zarić J, Ruegg C, Stevanović M. VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC. in Central European Journal of Biology. 2010;5(4):427-434.
doi:10.2478/s11535-010-0031-3 .

Petrović, Isidora, Nikčević, Gordana, Zarić, Jelena, Ruegg, Curzio, Stevanović, Milena, "VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC" in Central European Journal of Biology, 5, no. 4 (2010):427-434,
https://doi.org/10.2478/s11535-010-0031-3 . .

TY  - JOUR
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/359
AB  - The aim of this study has been to identify transcription factors involved in transcriptional regulation of the human SOX18 gene expression. Structural analysis revealed that the SOX18 promoter lacks a TATA box, but is CG-rich containing many putative binding sites for transcription factors that can bind and act through GC-boxes. Alignment analysis of promoter regions between human and mouse revealed conserved putative binding sites for transcription factors NF-Y and Sp-family members. Mithramycin A treatment led to increased SOX18 expression in vivo raising the possibility that the GC-rich sequence of the human SOX18 promoter might be occupied by transcription factor(s) that acts as repressor(s). Using in vitro binding assays we have demonstrated that transcription factors Sp3, ZBP-89 and NF-Y are capable of binding to the SOX18 promoter region spanning the sequence -200 to -162 relative to ATG and that formation of complexes could be efficiently reduced by mithramycin A. Furthermore, co-transfection experiments revealed that over-expression of Sp3 and ZBP-89 down-regulate, while over-expression of NF-Y up-regulates SOX18 promoter activity in HeLa cells. The involvement of these transcription factors in the regulation of SOX18 expression in HeLa cells was further confirmed in vivo by Western blot analyses. In this paper, for the first time, we have demonstrated that Sp3, ZBP-89 and NF-Y are involved in transcriptional regulation of the human SOX18 gene expression. Presented data provide the initial information about transcriptional regulation that will help in better understanding of molecular mechanisms involved in regulation of SOX18 gene expression.
PB  - Springer, Dordrecht
T2  - Molecular Biology Reports
T1  - ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells
EP  - 1000
IS  - 5
SP  - 993
VL  - 36
DO  - 10.1007/s11033-008-9272-x
ER  - 

@article{
author = "Petrović, Isidora and Kovačević Grujičić, Nataša and Stevanović, Milena",
year = "2009",
abstract = "The aim of this study has been to identify transcription factors involved in transcriptional regulation of the human SOX18 gene expression. Structural analysis revealed that the SOX18 promoter lacks a TATA box, but is CG-rich containing many putative binding sites for transcription factors that can bind and act through GC-boxes. Alignment analysis of promoter regions between human and mouse revealed conserved putative binding sites for transcription factors NF-Y and Sp-family members. Mithramycin A treatment led to increased SOX18 expression in vivo raising the possibility that the GC-rich sequence of the human SOX18 promoter might be occupied by transcription factor(s) that acts as repressor(s). Using in vitro binding assays we have demonstrated that transcription factors Sp3, ZBP-89 and NF-Y are capable of binding to the SOX18 promoter region spanning the sequence -200 to -162 relative to ATG and that formation of complexes could be efficiently reduced by mithramycin A. Furthermore, co-transfection experiments revealed that over-expression of Sp3 and ZBP-89 down-regulate, while over-expression of NF-Y up-regulates SOX18 promoter activity in HeLa cells. The involvement of these transcription factors in the regulation of SOX18 expression in HeLa cells was further confirmed in vivo by Western blot analyses. In this paper, for the first time, we have demonstrated that Sp3, ZBP-89 and NF-Y are involved in transcriptional regulation of the human SOX18 gene expression. Presented data provide the initial information about transcriptional regulation that will help in better understanding of molecular mechanisms involved in regulation of SOX18 gene expression.",
publisher = "Springer, Dordrecht",
journal = "Molecular Biology Reports",
title = "ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells",
pages = "1000-993",
number = "5",
volume = "36",
doi = "10.1007/s11033-008-9272-x"
}

Petrović, I., Kovačević Grujičić, N.,& Stevanović, M.. (2009). ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells. in Molecular Biology Reports
Springer, Dordrecht., 36(5), 993-1000.
https://doi.org/10.1007/s11033-008-9272-x

Petrović I, Kovačević Grujičić N, Stevanović M. ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells. in Molecular Biology Reports. 2009;36(5):993-1000.
doi:10.1007/s11033-008-9272-x .

Petrović, Isidora, Kovačević Grujičić, Nataša, Stevanović, Milena, "ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells" in Molecular Biology Reports, 36, no. 5 (2009):993-1000,
https://doi.org/10.1007/s11033-008-9272-x . .