Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity
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2015
Authors
Kojić, SnežanaNestorović, Aleksandra
Rakićević, Ljiljana
Protić, Olga
Jasnić, Jovana
Faulkner, Georgine
Radojković, Dragica
Article (Published version)
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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 intera...ction 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.
Keywords:
Stress response / p53 / Nkx2.5 / Heart / Apoptosis / Ankrd2Source:
Archives of Biochemistry and Biophysics, 2015, 569, 45-53Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- Collaborative Research Programme, ICGEB, Italy [CRP/YUG-05-01]
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (RS-MESTD-Basic Research (BR or ON)-173008)
DOI: 10.1016/j.abb.2015.02.001
ISSN: 0003-9861
PubMed: 25677450
WoS: 000352170300006
Scopus: 2-s2.0-84923369647
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .