TY  - JOUR
AU  - Jasnić, Jovana
AU  - Krause, Sabine
AU  - Savić, Slobodan
AU  - Kojić, Ana
AU  - Kovcić, Vlado
AU  - Bošković, Srđan
AU  - Nestorović, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Schreiber-Katz, Olivia
AU  - Vogel, Johannes G.
AU  - Schoser, Benedikt G.
AU  - Walter, Maggie C.
AU  - Valle, Giorgio
AU  - Radojković, Dragica
AU  - Faulkner, Georgine
AU  - Kojić, Snežana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/933
AB  - Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles.
PB  - Springer, New York
T2  - Histochemistry and Cell Biology
T1  - Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles
EP  - 584
IS  - 5
SP  - 569
VL  - 146
DO  - 10.1007/s00418-016-1465-0
ER  - 

@article{
author = "Jasnić, Jovana and Krause, Sabine and Savić, Slobodan and Kojić, Ana and Kovcić, Vlado and Bošković, Srđan and Nestorović, Aleksandra and Rakićević, Ljiljana and Schreiber-Katz, Olivia and Vogel, Johannes G. and Schoser, Benedikt G. and Walter, Maggie C. and Valle, Giorgio and Radojković, Dragica and Faulkner, Georgine and Kojić, Snežana",
year = "2016",
abstract = "Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles.",
publisher = "Springer, New York",
journal = "Histochemistry and Cell Biology",
title = "Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles",
pages = "584-569",
number = "5",
volume = "146",
doi = "10.1007/s00418-016-1465-0"
}

Jasnić, J., Krause, S., Savić, S., Kojić, A., Kovcić, V., Bošković, S., Nestorović, A., Rakićević, L., Schreiber-Katz, O., Vogel, J. G., Schoser, B. G., Walter, M. C., Valle, G., Radojković, D., Faulkner, G.,& Kojić, S.. (2016). Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles. in Histochemistry and Cell Biology
Springer, New York., 146(5), 569-584.
https://doi.org/10.1007/s00418-016-1465-0

Jasnić J, Krause S, Savić S, Kojić A, Kovcić V, Bošković S, Nestorović A, Rakićević L, Schreiber-Katz O, Vogel JG, Schoser BG, Walter MC, Valle G, Radojković D, Faulkner G, Kojić S. Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles. in Histochemistry and Cell Biology. 2016;146(5):569-584.
doi:10.1007/s00418-016-1465-0 .

Jasnić, Jovana, Krause, Sabine, Savić, Slobodan, Kojić, Ana, Kovcić, Vlado, Bošković, Srđan, Nestorović, Aleksandra, Rakićević, Ljiljana, Schreiber-Katz, Olivia, Vogel, Johannes G., Schoser, Benedikt G., Walter, Maggie C., Valle, Giorgio, Radojković, Dragica, Faulkner, Georgine, Kojić, Snežana, "Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles" in Histochemistry and Cell Biology, 146, no. 5 (2016):569-584,
https://doi.org/10.1007/s00418-016-1465-0 . .

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 . .

TY  - JOUR
AU  - Kojić, Snežana
AU  - Radojković, Dragica
AU  - Faulkner, Georgine
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/493
AB  - Remodeling is a stringently controlled process that enables adequate response of muscle cells to constant physical stresses. In this process, different kinds of stimuli have to be sensed and converted into biochemical signals that ultimately lead to alterations of muscle phenotype. Several multiprotein complexes located in the sarcomere and organized on the titin molecular spring have been identified as stress sensors and signal transducers. In this review, we focus on Ankrd1/CARP and Ankrd2/Arpp proteins, which belong to the muscle ankyrin repeat protein family (MARP) involved in a mechano-signaling pathway that links myofibrillar stress response to muscle gene expression. Apart from the mechanosensory function, they have an important role in transcriptional regulation, myofibrillar assembly, cardiogenesis and myogenesis. Their altered expression has been demonstrated in neuromuscular disorders, cardiovascular diseases, as well as in tumors, suggesting a role in pathological processes. Although analyzed in a limited number of patients, there is a considerable body of evidence that MARP proteins could be suitable candidates for prognostic and diagnostic biomarkers.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Critical Reviews in Clinical Laboratory Sciences
T1  - Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease
EP  - 294
IS  - 5-6
SP  - 269
VL  - 48
DO  - 10.3109/10408363.2011.643857
ER  - 

@article{
author = "Kojić, Snežana and Radojković, Dragica and Faulkner, Georgine",
year = "2011",
abstract = "Remodeling is a stringently controlled process that enables adequate response of muscle cells to constant physical stresses. In this process, different kinds of stimuli have to be sensed and converted into biochemical signals that ultimately lead to alterations of muscle phenotype. Several multiprotein complexes located in the sarcomere and organized on the titin molecular spring have been identified as stress sensors and signal transducers. In this review, we focus on Ankrd1/CARP and Ankrd2/Arpp proteins, which belong to the muscle ankyrin repeat protein family (MARP) involved in a mechano-signaling pathway that links myofibrillar stress response to muscle gene expression. Apart from the mechanosensory function, they have an important role in transcriptional regulation, myofibrillar assembly, cardiogenesis and myogenesis. Their altered expression has been demonstrated in neuromuscular disorders, cardiovascular diseases, as well as in tumors, suggesting a role in pathological processes. Although analyzed in a limited number of patients, there is a considerable body of evidence that MARP proteins could be suitable candidates for prognostic and diagnostic biomarkers.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Critical Reviews in Clinical Laboratory Sciences",
title = "Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease",
pages = "294-269",
number = "5-6",
volume = "48",
doi = "10.3109/10408363.2011.643857"
}

Kojić, S., Radojković, D.,& Faulkner, G.. (2011). Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease. in Critical Reviews in Clinical Laboratory Sciences
Taylor & Francis Ltd, Abingdon., 48(5-6), 269-294.
https://doi.org/10.3109/10408363.2011.643857

Kojić S, Radojković D, Faulkner G. Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease. in Critical Reviews in Clinical Laboratory Sciences. 2011;48(5-6):269-294.
doi:10.3109/10408363.2011.643857 .

Kojić, Snežana, Radojković, Dragica, Faulkner, Georgine, "Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease" in Critical Reviews in Clinical Laboratory Sciences, 48, no. 5-6 (2011):269-294,
https://doi.org/10.3109/10408363.2011.643857 . .

TY  - JOUR
AU  - Belgrano, Anna
AU  - Rakićević, Ljiljana
AU  - Mittempergher, Lorenza
AU  - Campanaro, Stefano
AU  - Martinelli, Valentina C.
AU  - Mouly, Vincent
AU  - Valle, Giorgio
AU  - Kojić, Snežana
AU  - Faulkner, Georgine
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/502
AB  - Background: Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors. Methodology/Principal Findings: Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-beta and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism. Conclusions/Significance: In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle
IS  - 10
VL  - 6
DO  - 10.1371/journal.pone.0025519
ER  - 

@article{
author = "Belgrano, Anna and Rakićević, Ljiljana and Mittempergher, Lorenza and Campanaro, Stefano and Martinelli, Valentina C. and Mouly, Vincent and Valle, Giorgio and Kojić, Snežana and Faulkner, Georgine",
year = "2011",
abstract = "Background: Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors. Methodology/Principal Findings: Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-beta and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism. Conclusions/Significance: In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle",
number = "10",
volume = "6",
doi = "10.1371/journal.pone.0025519"
}

Belgrano, A., Rakićević, L., Mittempergher, L., Campanaro, S., Martinelli, V. C., Mouly, V., Valle, G., Kojić, S.,& Faulkner, G.. (2011). Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle. in PLoS One
Public Library Science, San Francisco., 6(10).
https://doi.org/10.1371/journal.pone.0025519

Belgrano A, Rakićević L, Mittempergher L, Campanaro S, Martinelli VC, Mouly V, Valle G, Kojić S, Faulkner G. Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle. in PLoS One. 2011;6(10).
doi:10.1371/journal.pone.0025519 .

Belgrano, Anna, Rakićević, Ljiljana, Mittempergher, Lorenza, Campanaro, Stefano, Martinelli, Valentina C., Mouly, Vincent, Valle, Giorgio, Kojić, Snežana, Faulkner, Georgine, "Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle" in PLoS One, 6, no. 10 (2011),
https://doi.org/10.1371/journal.pone.0025519 . .