ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression

Schaeffer, Etienne; Vigneron, Marc; Sibler, Annie-Paule; Oulad‐Abdelghani, Mustapha; Chatton, Bruno; Donzeau, Mariel

doi:10.1080/15384101.2015.1064568

Cited by 5 publications

(10 citation statements)

References 53 publications

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“…The Ccnd1 gene is regulated at the transcriptional and translational levels (27)(28)(29). We found that Ccnd1 transcription is dependent on Insm1 dosage, and the protein level is also decreased in b-cells of Insm +/lacZ mice.…”

Section: Discussionmentioning

confidence: 74%

Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass

Wei

Zhang

et al. 2018

Diabetes

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Baseline b-cell mass is established during the early postnatal period when b-cells expand. In this study, we show that heterozygous ablation of Insm1 decreases baseline b-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an ob/ob background, glucose intolerance was more severe in Insm1 +/lacZ mice compared with Insm1 +/+ mice, although no further decrease in the b-cell mass was detected. In islets of early postnatal Insm1 +/lacZ mice, the cell cycle was prolonged in b-cells due to downregulation of the cell cycle gene Ccnd1. Although Insm1 had a low affinity for the Ccnd1 promoter compared with other binding sites, binding affinity was strongly dependent on Insm1 levels. We observed dramatically decreased binding of Insm1 to the Ccnd1 promoter after downregulation of Insm1 expression. Furthermore, downregulation of Ccnd1 resulted in a prolonged cell cycle, and overexpression of Ccnd1 rescued cell cycle abnormalities observed in Insm1-deficient b-cells. We conclude that decreases in Insm1 interfere with b-cell specification during the early postnatal period and impair glucose homeostasis during metabolic stress in adults. Insm1 levels are therefore a factor that can influence the development of diabetes.Pancreatic b-cell mass is regulated both during development and in the adult. Lineage tracing in animals indicates that embryonic b-cells mainly differentiate from pancreatic progenitor cells (1), whereas postnatal increases in b-cell mass arise through self-renewal (2,3). b-Cell replication slows considerably in adults, although variations in insulin demand can lead to adaptive changes in b-cell mass (4). Sufficient b-cell mass is essential for normal regulation of blood glucose levels. Loss of b-cell mass by an immune attack or metabolic stressors results in type 1 and type 2 diabetes, respectively. In addition, although b-cell mass varies in individuals, low b-cell mass is a risk factor for prediabetes and diabetes (5). At least two factors contribute to total b-cell mass: replication capacity and baseline b-cell mass. The replication rate of adult b-cells is low, and massive efforts have been made to restore diabetic b-cell loss by enhancing b-cell replication. In contrast, the establishment of the baseline b-cell mass is not well investigated, and it is not yet fully understood how postnatal b-cell expansion varies in different individuals.The baseline b-cell mass is established in the early postnatal period in both mice and humans (2,6-8). Recent identified factors that modulate the postnatal b-cell expansion regulate the metabolic pathways or the cell cycle (9-11). The cyclin genes Ccnd1 and Ccnd2 are essential for postnatal b-cell growth and regulate the progression through G 1 through interaction with . Heterozygous mutations in Ccnd1 combined with complete knockout of Ccnd2 have dose-dependent effects on b-cell mass (14). Cell cycle inhibitors are another group of essential regulators in the postnatal b-cell mass expansion. p16 INK4a is a b-cell replication inhibi...

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Section: Discussionmentioning

confidence: 74%

Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass

Wei

Zhang

et al. 2018

Diabetes

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“…Notably, there is increasing evidence indicating that ATF7 may function to regulate proliferation and the cell cycle in various cancers. For example, ATF7 was shown to promote cell cycle progression by regulating cyclin D1, as well as the expression of stress‐activated MAPK in G1 and S phases and Cdk1‐cyclin B1 in the G2/M phase . In addition, ATF7 has been shown to form a heterodimeric complex with the AP‐1 family member, c‐jun, through its C‐terminal leucine‐zipper region, which functions to promote cell growth .…”

Section: Discussionmentioning

confidence: 99%

“…For example, ATF7 was shown to promote cell cycle progression by regulating cyclin D1, as well as the expression of stress-activated MAPK in G1 and S phases and Cdk1-cyclin B1 in the G2/M phase. 26,27 In addition, ATF7 has been shown to form a heterodimeric complex with the AP-1 family member, c-jun, through its C-terminal leucine-zipper region, which functions to promote cell growth. 28 Mouse knockout studies have further shown that ATF7 knockout, combined with key mutations in ATF2, results in embryonic lethality that is characterized by high levels of apoptosis in developing hepatocytes and hematopoietic cells.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus‐regulated growth of liver cancer cells occurs through the microRNA‐340‐5p‐activating transcription factor 7‐heat shock protein A member 1B axis

et al. 2019

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Hepatocellular carcinoma ( HCC ) is a common cancer with poor prognosis. Hepatitis B virus ( HBV ) is one of the leading causes of HCC , but the precise mechanisms by which this infection promotes cancer development are not fully understood. Recently, miR‐340‐5p, a micro RNA (mi RNA ) that has been identified as a cancer suppressor gene, was found to inhibit the migration and invasion of liver cancer cells. However, the effect of miR‐340‐5p on cell proliferation and apoptosis in HBV ‐associated HCC remains unknown. In our study, we show that miR‐340‐5p plays an important role during HBV infection and hepatocellular carcinoma development. Specifically, this mi RNA directly binds to the mRNA encoding activating transcription factor 7 ( ATF 7), a protein that both promotes cell proliferation and suppresses apoptosis through its interaction with heat shock protein A member 1B ( HSPA 1B). We further found that miR‐340‐5p is downregulated by HBV , which enhances ATF 7 expression, leading to enhanced cell proliferation and inhibition of apoptosis. Notably, ATF 7 is upregulated in HCC tissue, suggesting that HBV may target miR‐340‐5p in vivo to promote ATF 7/ HSPA 1B‐mediated proliferation and apoptosis and regulate liver cancer progression. This work helps to elucidate the complex interactions between HBV and host mi RNA s and further suggests that miR‐340‐5p may represent a promising candidate for the development of improved therapeutic strategies for HCC .

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“…Finally, a monoclonal antibody (mAb) directed against the activating transcription factor 7 (ATF7) was chemically coupled to a thiol-containing synthetic E3 peptide. This antibody was chosen because it recognizes endogenous ATF7 (1A7) bound to the chromatin .…”

Section: Resultsmentioning

confidence: 99%

“…The co-localized signal was dependent of the specific interaction between E3 and K3 peptides as no signal was detectable in the presence of an unrelated V H H without K3 or in the absence of con1-mCherry-E3 expression. Finally, a monoclonal antibody (mAb) directed against the activating transcription factor 7 (ATF7) 21 was chemically coupled to a thiol-containing synthetic E3 peptide. This antibody was chosen because it recognizes endogenous ATF7 (1A7) 22 bound to the chromatin.…”

Section: In Cellulo Conjugation Of Macromolecules Via E3 and K3 Peptidesmentioning

confidence: 99%

Self-Associating Peptides for Modular Bifunctional Conjugation of Tetramer Macromolecules in Living Cells

et al. 2019

Self Cite

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Monitoring the assembly of macromolecules to design entities with novel properties can be achieved either chemically creating covalent bonds or by non-covalent connections using appropriate structural motifs. In this report, two self-associating peptides (named K3 and E3) that originate from p53 tetramerization domain were developed as tools for highly specific and non-covalent heterotetramerization of two bio-molecules. The pairing/coupling preferences of K3 and E3 were first evaluated by molecular modeling data and confirmed using circular dichroism spectroscopy, size-exclusion chromatography and biological assays. Regardless of the moieties fused to K3 and E3, these two peptides self-assembled into dimers of dimers to form bivalent heterotetrameric complexes that proved to be extremely stable inside of living cells. The benefits of the multivalency in terms of avidity, specificity and expanded functional activity were strikingly revealed when the Proliferating Cell Nuclear Antigen (PCNA), which is essential for DNA replication, was targeted using a heterotetramer presenting both an antibody fragment against PCNA and a specific PCNA binder peptide. In vitro heterotetramerization of these two known PCNA ligands increased their binding efficiencies to PCNA up to 80-fold compared to the best homotetramer counterpart. In cellulo, the heterotetramers were able to efficiently inhibit DNA replication and to trigger cell death. Altogether, we demonstrate that these two bi-selective self-assembling peptidic domains offer a versatile non-covalent conjugation method that can be easily implemented for protein engineering.

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ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression

Cited by 5 publications

References 53 publications

Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass

Haploinsufficiency of Insm1 Impairs Postnatal Baseline β-Cell Mass

Hepatitis B virus‐regulated growth of liver cancer cells occurs through the microRNA‐340‐5p‐activating transcription factor 7‐heat shock protein A member 1B axis

Self-Associating Peptides for Modular Bifunctional Conjugation of Tetramer Macromolecules in Living Cells

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