ICGEB, Italy [CRP/YUG-05-01]

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ICGEB, Italy [CRP/YUG-05-01]

Authors

Publications

Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease

Kojić, Snežana; Radojković, Dragica; Faulkner, Georgine

(Taylor & Francis Ltd, Abingdon, 2011)

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 . .
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Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle

Belgrano, Anna; Rakićević, Ljiljana; Mittempergher, Lorenza; Campanaro, Stefano; Martinelli, Valentina C.; Mouly, Vincent; Valle, Giorgio; Kojić, Snežana; Faulkner, Georgine

(Public Library Science, San Francisco, 2011)

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 . .
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Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze

Kojić, Snežana

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2010)

TY  - JOUR
AU  - Kojić, Snežana
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/456
AB  - Familiju MARP (muscle ankyrin repeat proteins) čine tri strukturno slična proteina: CARP/Ankrd1, Ankrd2/Arpp i DARP/Ankrd23. Sva tri proteina poseduju ankirinske ponovke preko kojih ostvaruju protein-protein interakcije kao i signal za lokalizaciju u jedru. Članovi familije MARP imaju strukturnu i regulatornu funkciju i mogu biti lokalizovani i u jedru i u citoplazmi mišićne ćelije. Učestvuju u signalnoj transdukciji kao molekulski glasnici koji prenose informacije mehaničkog stresa sa sarkomere do jedra, gde učestvuju u regulaciji genske ekspresije. Nivo proteina CARP/Ankrd1 i Ankrd2/Arpp je izmenjen u mišićnim bolestima koje karakteriše atrofija mišića, kao što su Dišenova mišićna distrofija, kongenitalna miopatija i spinalna mišićna atrofija. Mutacije u genu za CARP/Ankrd1 su otkrivene u pacijenata sa dilatiranom i hipertrofičnom kardiomiopatijom. Promene u ekspresiji ovih proteina su takođe uočene u tumorima kao što su rabdomiosarkom, onkocitom bubrega i kancer ovarijuma. U cilju funkcionalne karakterizacije proteina familije MARP, pokazali smo da oba proteina interaguju sa supresorom tumora p53, a geni za CARP/Ankrd1 i Ankrd2/Arpp su pozitivno regulisani ovim transkripcionim faktorom. Rezultati su ukazali na moguću ulogu proteina CARP/Ankrd1 i Ankrd2/Arpp u molekularnim mehanizmima tumorogeneze, čime se otvara novo polje istraživanja ove familije proteina.
AB  - The MARP (muscle ankyrin repeat protein) family comprises three structurally similar proteins: CARP/Ankrd1, Ankrd2/Arpp and DARP/Ankrd23. They share four conserved copies of 33-residue ankyrin repeats and contain a nuclear localization signal, allowing the sorting of MARPs to the nucleus. They are found both in the nucleus and in the cytoplasm of skeletal and cardiac muscle cells, suggesting that MARPs shuttle within the cell enabling them to play a role in signal transduction in striated muscle. Expression of MARPs is altered under different pathological conditions. In skeletal muscle, CARP/Ankrd1 and Ankrd2/Arpp are up-regulated in muscle in patients suffering from Duchene muscular dystrophy, congenital myopathy and spinal muscular atrophy. Mutations in Ankrd1 gene (coding CARP/Ankrd1) were identified in dilated and hypertrophic cardiomyopathies. Altered expression of MARPs is also observed in rhabdomyosarcoma, renal oncocytoma and ovarian cancer. In order to functionally characterize MARP family members CARP/Ankrd1 and Ankrd2/Arpp, we have found that both proteins interact with the tumor suppressor p53 both in vivo and in vitro and that p53 up-regulates their expression. Our results implicate the potential role of MARPs in molecular mechanisms relevant to tumor response and progression.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze
T1  - MARP protein family: A possible role in molecular mechanisms of tumorigenesis
EP  - 164
IS  - 3
SP  - 157
VL  - 29
DO  - 10.2478/v10011-010-0024-9
ER  - 
@article{
author = "Kojić, Snežana",
year = "2010",
abstract = "Familiju MARP (muscle ankyrin repeat proteins) čine tri strukturno slična proteina: CARP/Ankrd1, Ankrd2/Arpp i DARP/Ankrd23. Sva tri proteina poseduju ankirinske ponovke preko kojih ostvaruju protein-protein interakcije kao i signal za lokalizaciju u jedru. Članovi familije MARP imaju strukturnu i regulatornu funkciju i mogu biti lokalizovani i u jedru i u citoplazmi mišićne ćelije. Učestvuju u signalnoj transdukciji kao molekulski glasnici koji prenose informacije mehaničkog stresa sa sarkomere do jedra, gde učestvuju u regulaciji genske ekspresije. Nivo proteina CARP/Ankrd1 i Ankrd2/Arpp je izmenjen u mišićnim bolestima koje karakteriše atrofija mišića, kao što su Dišenova mišićna distrofija, kongenitalna miopatija i spinalna mišićna atrofija. Mutacije u genu za CARP/Ankrd1 su otkrivene u pacijenata sa dilatiranom i hipertrofičnom kardiomiopatijom. Promene u ekspresiji ovih proteina su takođe uočene u tumorima kao što su rabdomiosarkom, onkocitom bubrega i kancer ovarijuma. U cilju funkcionalne karakterizacije proteina familije MARP, pokazali smo da oba proteina interaguju sa supresorom tumora p53, a geni za CARP/Ankrd1 i Ankrd2/Arpp su pozitivno regulisani ovim transkripcionim faktorom. Rezultati su ukazali na moguću ulogu proteina CARP/Ankrd1 i Ankrd2/Arpp u molekularnim mehanizmima tumorogeneze, čime se otvara novo polje istraživanja ove familije proteina., The MARP (muscle ankyrin repeat protein) family comprises three structurally similar proteins: CARP/Ankrd1, Ankrd2/Arpp and DARP/Ankrd23. They share four conserved copies of 33-residue ankyrin repeats and contain a nuclear localization signal, allowing the sorting of MARPs to the nucleus. They are found both in the nucleus and in the cytoplasm of skeletal and cardiac muscle cells, suggesting that MARPs shuttle within the cell enabling them to play a role in signal transduction in striated muscle. Expression of MARPs is altered under different pathological conditions. In skeletal muscle, CARP/Ankrd1 and Ankrd2/Arpp are up-regulated in muscle in patients suffering from Duchene muscular dystrophy, congenital myopathy and spinal muscular atrophy. Mutations in Ankrd1 gene (coding CARP/Ankrd1) were identified in dilated and hypertrophic cardiomyopathies. Altered expression of MARPs is also observed in rhabdomyosarcoma, renal oncocytoma and ovarian cancer. In order to functionally characterize MARP family members CARP/Ankrd1 and Ankrd2/Arpp, we have found that both proteins interact with the tumor suppressor p53 both in vivo and in vitro and that p53 up-regulates their expression. Our results implicate the potential role of MARPs in molecular mechanisms relevant to tumor response and progression.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze, MARP protein family: A possible role in molecular mechanisms of tumorigenesis",
pages = "164-157",
number = "3",
volume = "29",
doi = "10.2478/v10011-010-0024-9"
}
Kojić, S.. (2010). Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 29(3), 157-164.
https://doi.org/10.2478/v10011-010-0024-9
Kojić S. Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze. in Journal of Medical Biochemistry. 2010;29(3):157-164.
doi:10.2478/v10011-010-0024-9 .
Kojić, Snežana, "Proteini familije MARP - moguća uloga u molekularnim mehanizmima tumorogeneze" in Journal of Medical Biochemistry, 29, no. 3 (2010):157-164,
https://doi.org/10.2478/v10011-010-0024-9 . .
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