A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein

Kojić, Snežana; Nestorovic, Aleksandra; Rakićević, Ljiljana; Belgrano, Anna; Stanković, Marija; Divac, Aleksandra; Faulkner, Georgine

doi:10.1016/j.abb.2010.06.029

Cited by 69 publications

(73 citation statements)

References 41 publications

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“…To test this hypothesis, we performed luciferase assays using the MLC-2v promoter and the p53 responsive promoter. CARP repressed MLC-2v promoter activity in neonatal rat cardiomyocytes and promoted p53 responsive promoter activity in HEK 293 cells, consistent with previous reports (Zou et al, 1997;Kojic et al, 2010). The non-phosphorylatable form of CARP had a stronger effect than the WT form (Fig.…”

Section: Carp Regulates Cardiac Cellular Functions Depending On Its Psupporting

confidence: 82%

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Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart

Yura

Amano

Takefuji

et al. 2016

Cell Struct. Funct.

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ABSTRACT. Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography. First, we examined protein phosphorylation by extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), which has been relatively well studied in cardiomyocytes. The KISS method showed that ERK and PKA mediated the phosphorylation of known cardiac-substrates of each kinase such as Rps6ka1 and cTnI, respectively. Using this method, we found about 330 proteins as Rho-kinase-mediated substrates, whose substrate in cardiomyocytes is unknown. Among them, CARP/Ankrd1, a muscle ankyrin repeat protein, was confirmed as a novel Rho-kinasemediated substrate. We also found that non-phosphorylatable form of CARP repressed cardiac hypertrophyrelated gene Myosin light chain-2v (MLC-2v) promoter activity, and decreased cell size of heart derived H9c2 myoblasts more efficiently than wild type-CARP. Thus, focused proteomics enable us to reveal a novel signaling pathway in the heart.

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Section: Carp Regulates Cardiac Cellular Functions Depending On Its Psupporting

confidence: 82%

“…CARP has been described not only as a negative regulator of MLC-2v promoter activity (Zou et al, 1997) but also as a positive regulator of p53 responsive promoter activity (Kojic et al, 2010). Thus, we speculated that CARP changes the promoter activity depending on its phosphorylation state.…”

Section: Carp Regulates Cardiac Cellular Functions Depending On Its Pmentioning

confidence: 86%

Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart

Yura

Amano

Takefuji

et al. 2016

Cell Struct. Funct.

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“…In the sarcomere, ANKRD1 is a titin-associated structural component that, together with myopalladin, calpain protease p94, and Q39 calsequestrin, forms a complex that appears to be critical for sarcomere stability of differentiating cardiomyocytes in vitro. 3,4,20,21 Reduction of Ankrd1 mRNA and protein in rat cardiomyocytes by siRNA or doxorubicin leads to sarcomere disintegration and myofibrillar disarray, 20 presumably due to a combination of loss of ANKRD1 from the I-band complex and reduced expression of a range of ANKRD1 transcriptional targets. It has also been suggested that members of the MARP family serve a role in the muscle cell as part of a mechanosensory apparatus, in which MARPs act as shuttles to transport factors, such as Tp53, to the nucleus.…”

Section: Cellular Actions Of Ankrd1mentioning

confidence: 99%

“…3 Desmin is another cytoplasmic partner whose depletion leads to up-regulation of Ankrd1. 23 The MARPs are associated with several aspects of transcriptional control in striated muscle, including associations with YB-1, 18 Tp53, 16,21 and nucleolin. 16 Early developmental studies showed that the high-level expression of Ankrd1 was associated with down-regulation of myocyte proteins by association with YB-1.…”

Section: Cellular Actions Of Ankrd1mentioning

confidence: 99%

“…It has also been suggested that members of the MARP family serve a role in the muscle cell as part of a mechanosensory apparatus, in which MARPs act as shuttles to transport factors, such as Tp53, to the nucleus. 3,21,22 The MARP proteins may also shuttle between cytoplasm and nucleus as part of a stress-related regulatory pathway. We have recently observed that ANKRD1 is involved in the transport of GATA On the basis of many foregoing studies, depletion of ANKRD1 could be expected to affect both cytoplasmic and nuclear processes.…”

Section: Cellular Actions Of Ankrd1mentioning

confidence: 99%

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Global Deletion of Ankrd1 Results in a Wound-Healing Phenotype Associated with Dermal Fibroblast Dysfunction

Samaras

Almodóvar-García

et al. 2015

The American Journal of Pathology

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The expression of ankyrin repeat domain protein 1 (Ankrd1), a transcriptional cofactor and sarcomeric component, is strongly elevated by wounding and tissue injury. We developed a conditional Ankrd1(fl/fl) mouse, performed global deletion with Sox2-cre, and assessed the role of this protein in cutaneous wound healing. Although global deletion of Ankrd1 did not affect mouse viability or development, Ankrd1(-/-) mice had at least two significant wound-healing phenotypes: extensive necrosis of ischemic skin flaps, which was reversed by adenoviral expression of ANKRD1, and delayed excisional wound closure, which was characterized by decreased contraction and reduced granulation tissue thickness. Skin fibroblasts isolated from Ankrd1(-/-) mice did not spread or migrate on collagen- or fibronectin-coated surfaces as efficiently as fibroblasts isolated from Ankrd1(fl/fl) mice. More important, Ankrd1(-/-) fibroblasts failed to contract three-dimensional floating collagen gels. Reconstitution of ANKRD1 by adenoviral infection stimulated both collagen gel contraction and actin fiber organization. These in vitro data were consistent with in vivo wound closure studies, and suggest that ANKRD1 is important for the proper interaction of fibroblasts with a compliant collagenous matrix both in vitro and in vivo.

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