TY  - JOUR
AU  - Jasnić, Jovana
AU  - Nestorović, Aleksandra
AU  - Savić, Slobodan
AU  - Karasek, Sinisa
AU  - Vitulo, Nicola
AU  - Valle, Giorgio
AU  - Faulkner, Georgine
AU  - Radojković, Dragica
AU  - Kojić, Snežana
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/814
AB  - Muscle-specific mechanosensors Ankrd2/Arpp (ankyrin repeat protein 2) and Ankrd1/CARP (cardiac ankyrin repeat protein) have an important role in transcriptional regulation, myofibrillar assembly, cardiogenesis and myogenesis. In skeletal muscle myofibrils, Ankrd2 has a structural role as a component of a titin associated stretch-sensing complex, while in the nucleus it exerts regulatory function as transcriptional co-factor. It is also involved in myogenic differentiation and coordination of myoblast proliferation. Although expressed in the heart, the role of Ankrd2 in the cardiac muscle is completely unknown. Recently, we have shown that hypertrophic and dilated cardiomyopathy pathways are altered upon Ankrd2 silencing suggesting the importance of this protein in cardiac tissue. Here we provide the underlying basis for the functional investigation of Ankrd2 in the heart. We confirmed reduced Ankrd2 expression levels in human heart in comparison with Ankrd1 using RNAseq and Western blot. For the first time we demonstrated that, apart from the sarcomere and nucleus, both proteins are localized to the intercalated disks of human cardiomyocytes. We further tested the expression and localization of endogenous Ankrd2 in rat neonatal cardiomyocytes, a well-established model for studying cardiac-specific proteins. Ankrd2 was found to be expressed in both the cytoplasm and nucleus, independently from maturation status of cardiomyocytes. In contrast to Ankrd1, it is not responsive to the cardiotoxic drug Doxorubicin, suggesting that different mechanisms govern their expression in cardiac cells.
PB  - Springer, New York
T2  - Histochemistry and Cell Biology
T1  - Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes
EP  - 597
IS  - 6
SP  - 583
VL  - 143
DO  - 10.1007/s00418-015-1307-5
ER  - 

@article{
author = "Jasnić, Jovana and Nestorović, Aleksandra and Savić, Slobodan and Karasek, Sinisa and Vitulo, Nicola and Valle, Giorgio and Faulkner, Georgine and Radojković, Dragica and Kojić, Snežana",
year = "2015",
abstract = "Muscle-specific mechanosensors Ankrd2/Arpp (ankyrin repeat protein 2) and Ankrd1/CARP (cardiac ankyrin repeat protein) have an important role in transcriptional regulation, myofibrillar assembly, cardiogenesis and myogenesis. In skeletal muscle myofibrils, Ankrd2 has a structural role as a component of a titin associated stretch-sensing complex, while in the nucleus it exerts regulatory function as transcriptional co-factor. It is also involved in myogenic differentiation and coordination of myoblast proliferation. Although expressed in the heart, the role of Ankrd2 in the cardiac muscle is completely unknown. Recently, we have shown that hypertrophic and dilated cardiomyopathy pathways are altered upon Ankrd2 silencing suggesting the importance of this protein in cardiac tissue. Here we provide the underlying basis for the functional investigation of Ankrd2 in the heart. We confirmed reduced Ankrd2 expression levels in human heart in comparison with Ankrd1 using RNAseq and Western blot. For the first time we demonstrated that, apart from the sarcomere and nucleus, both proteins are localized to the intercalated disks of human cardiomyocytes. We further tested the expression and localization of endogenous Ankrd2 in rat neonatal cardiomyocytes, a well-established model for studying cardiac-specific proteins. Ankrd2 was found to be expressed in both the cytoplasm and nucleus, independently from maturation status of cardiomyocytes. In contrast to Ankrd1, it is not responsive to the cardiotoxic drug Doxorubicin, suggesting that different mechanisms govern their expression in cardiac cells.",
publisher = "Springer, New York",
journal = "Histochemistry and Cell Biology",
title = "Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes",
pages = "597-583",
number = "6",
volume = "143",
doi = "10.1007/s00418-015-1307-5"
}

Jasnić, J., Nestorović, A., Savić, S., Karasek, S., Vitulo, N., Valle, G., Faulkner, G., Radojković, D.,& Kojić, S.. (2015). Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes. in Histochemistry and Cell Biology
Springer, New York., 143(6), 583-597.
https://doi.org/10.1007/s00418-015-1307-5

Jasnić J, Nestorović A, Savić S, Karasek S, Vitulo N, Valle G, Faulkner G, Radojković D, Kojić S. Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes. in Histochemistry and Cell Biology. 2015;143(6):583-597.
doi:10.1007/s00418-015-1307-5 .

Jasnić, Jovana, Nestorović, Aleksandra, Savić, Slobodan, Karasek, Sinisa, Vitulo, Nicola, Valle, Giorgio, Faulkner, Georgine, Radojković, Dragica, Kojić, Snežana, "Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes" in Histochemistry and Cell Biology, 143, no. 6 (2015):583-597,
https://doi.org/10.1007/s00418-015-1307-5 . .

TY  - JOUR
AU  - Kojić, Snežana
AU  - Nestorović, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Protić, Olga
AU  - Jasnić, Jovana
AU  - Faulkner, Georgine
AU  - Radojković, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/879
AB  - Transcription factor Nkx2.5, essential for heart development, regulates cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted (GATA4 and dHAND) or ubiquitous (p300) transcription regulators. Here we demonstrate that Nkx2.5 and p53 synergistically activate the promoter of the striated muscle stress responsive transcriptional cofactor Ankrd2, involved in coordination of proliferation and apoptosis during myogenic differentiation. Moreover, the p53 protein is able to interact with both wild type Nkx2.5 and its mutant Delta Nkx2.5 (aa 1-198) found in patients with diverse cardiac malformations. Nkx2.5 interaction site of p53 maps to the C terminal region, while p53 binding site on Nkx2.5 lies outside its C terminus. In addition, overexpression of Nkx2.5 has a modulatory, promoter dependent effect on p53 transactivation, while the mutant significantly abolished p53 activity on the Mdm2, p21(WAF1/CIP1) and Box promoters. Their physical interaction contributes to the observed behavior in the case of the Mdm2 promoter. Our data provide a new evidence for the role of p53 in cardiac function through interaction with Nkx2.5.
PB  - Elsevier Science Inc, New York
T2  - Archives of Biochemistry and Biophysics
T1  - Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity
EP  - 53
SP  - 45
VL  - 569
DO  - 10.1016/j.abb.2015.02.001
ER  - 

@article{
author = "Kojić, Snežana and Nestorović, Aleksandra and Rakićević, Ljiljana and Protić, Olga and Jasnić, Jovana and Faulkner, Georgine and Radojković, Dragica",
year = "2015",
abstract = "Transcription factor Nkx2.5, essential for heart development, regulates cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted (GATA4 and dHAND) or ubiquitous (p300) transcription regulators. Here we demonstrate that Nkx2.5 and p53 synergistically activate the promoter of the striated muscle stress responsive transcriptional cofactor Ankrd2, involved in coordination of proliferation and apoptosis during myogenic differentiation. Moreover, the p53 protein is able to interact with both wild type Nkx2.5 and its mutant Delta Nkx2.5 (aa 1-198) found in patients with diverse cardiac malformations. Nkx2.5 interaction site of p53 maps to the C terminal region, while p53 binding site on Nkx2.5 lies outside its C terminus. In addition, overexpression of Nkx2.5 has a modulatory, promoter dependent effect on p53 transactivation, while the mutant significantly abolished p53 activity on the Mdm2, p21(WAF1/CIP1) and Box promoters. Their physical interaction contributes to the observed behavior in the case of the Mdm2 promoter. Our data provide a new evidence for the role of p53 in cardiac function through interaction with Nkx2.5.",
publisher = "Elsevier Science Inc, New York",
journal = "Archives of Biochemistry and Biophysics",
title = "Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity",
pages = "53-45",
volume = "569",
doi = "10.1016/j.abb.2015.02.001"
}

Kojić, S., Nestorović, A., Rakićević, L., Protić, O., Jasnić, J., Faulkner, G.,& Radojković, D.. (2015). Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity. in Archives of Biochemistry and Biophysics
Elsevier Science Inc, New York., 569, 45-53.
https://doi.org/10.1016/j.abb.2015.02.001

Kojić S, Nestorović A, Rakićević L, Protić O, Jasnić J, Faulkner G, Radojković D. Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity. in Archives of Biochemistry and Biophysics. 2015;569:45-53.
doi:10.1016/j.abb.2015.02.001 .

Kojić, Snežana, Nestorović, Aleksandra, Rakićević, Ljiljana, Protić, Olga, Jasnić, Jovana, Faulkner, Georgine, Radojković, Dragica, "Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity" in Archives of Biochemistry and Biophysics, 569 (2015):45-53,
https://doi.org/10.1016/j.abb.2015.02.001 . .

TY  - JOUR
AU  - Martinelli, Valentina C.
AU  - Kyle, W. Buck
AU  - Kojić, Snežana
AU  - Vitulo, Nicola
AU  - Li, Zhaohui
AU  - Belgrano, Anna
AU  - Maiuri, Paolo
AU  - Banks, Lawrence
AU  - Vatta, Matteo
AU  - Valle, Giorgio
AU  - Faulkner, Georgine
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/780
AB  - ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle
IS  - 3
VL  - 9
DO  - 10.1371/journal.pone.0092259
ER  - 

@article{
author = "Martinelli, Valentina C. and Kyle, W. Buck and Kojić, Snežana and Vitulo, Nicola and Li, Zhaohui and Belgrano, Anna and Maiuri, Paolo and Banks, Lawrence and Vatta, Matteo and Valle, Giorgio and Faulkner, Georgine",
year = "2014",
abstract = "ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle",
number = "3",
volume = "9",
doi = "10.1371/journal.pone.0092259"
}

Martinelli, V. C., Kyle, W. B., Kojić, S., Vitulo, N., Li, Z., Belgrano, A., Maiuri, P., Banks, L., Vatta, M., Valle, G.,& Faulkner, G.. (2014). ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle. in PLoS One
Public Library Science, San Francisco., 9(3).
https://doi.org/10.1371/journal.pone.0092259

Martinelli VC, Kyle WB, Kojić S, Vitulo N, Li Z, Belgrano A, Maiuri P, Banks L, Vatta M, Valle G, Faulkner G. ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle. in PLoS One. 2014;9(3).
doi:10.1371/journal.pone.0092259 .

Martinelli, Valentina C., Kyle, W. Buck, Kojić, Snežana, Vitulo, Nicola, Li, Zhaohui, Belgrano, Anna, Maiuri, Paolo, Banks, Lawrence, Vatta, Matteo, Valle, Giorgio, Faulkner, Georgine, "ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle" in PLoS One, 9, no. 3 (2014),
https://doi.org/10.1371/journal.pone.0092259 . .