CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication

Mansilla, Sabrina F.; Vega, María Belén de la; Calzetta, Nicolás Luis; Siri, Sebastián Omar; Gottifredi, Vanesa

doi:10.3390/genes11060593

Cited by 78 publications

(55 citation statements)

References 125 publications

(246 reference statements)

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“…Those inhibitors share a homologous N-terminal domain, which contains a cyclin-binding motif 1(Cy1). This motif is indispensable for the inhibition property of p21 Cip1/Waf1, which allows p21 Cip1/Waf1 binding to CDK in a region that blocks its ability to complex with cyclins, and thus prevents CDK activation [ 26 , 27 ]. Besides a direct interaction with the CDK2 complex, the Cy1 motif in p21 Cip1/Waf1 mediates cell cycle arrest also through the completion with other cell cycle regulators.…”

Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

“…Furthermore, p21 Cip1/Waf1 can regulate cell proliferation by interacting with the PCNA, a DNA polymerase accessory factor, which plays a regulatory role in the S phase. PCNA is a regulator of DNA synthesis, and its expression is controlled by E2F (E2 factor) transcriptional factor containing complexes [ 27 ]. Interaction between p21 Cip1/Waf1 and PCNA ensures the progress of the cell cycle.…”

Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

“…p21 Cip1/Waf1 displaces PCNA partners to control DNA replication in the S phase. In return, PCNA also controls the expression of p21 Cip1/Waf1 in the S phase to prevent the upregulation of p21 Cip1/Waf1 , which arrests the cell cycle [ 27 ]. Besides, DNA damage causes p21 Cip1/Waf1 to bind CDK1 complexes, which inhibits the catalytic function of the complex, subsequently bringing about cell cycle arrest [ 41 , 42 ].…”

Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

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The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

Lai

Shin

Qiu

2020

IJMS

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The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.

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Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

Section: Cdk20 and P21 Cip1/waf1 In Cell Cyclementioning

confidence: 99%

See 1 more Smart Citation

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

Lai

Shin

Qiu

2020

IJMS

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“…It plays a key role in regulating the transition of cells from G1 to S phase and from G2 to M phase. 53 In the study by Shu et al 30 of RKO and MCF7 cells, RBM38 was required to maintain the stability of the p53induced expression of p21 transcript. After DNA damage, p53 first mediates the elevation of RBM38 expression, which can then induce high levels of p21 expression.…”

Section: Rbm38 Induces Cell Cycle Arrest By Stabilizing the P21 Transmentioning

confidence: 99%

“…It plays a key role in regulating the transition of cells from G1 to S phase and from G2 to M phase. 53 …”

Section: The Regulatory Mechanism Of Rbm38mentioning

confidence: 99%

RNA-Binding Motif Protein 38 as a Potential Biomarker and Therapeutic Target in Cancer

She¹,

Lin²,

Liang³

et al. 2020

OTT

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RNA-binding proteins (RBPs) act as a key factor in gene regulation by governing RNA metabolism. They contribute to the expression and functions of most RNAs by binding to them and forming complexes. RNA-binding motif protein 38 (RBM38), a member of the RBP family, alters the stability and translation of targeted mRNAs to affect various biological processes, such as cell proliferation, cell cycle arrest, and myogenic differentiation. RBM38 contains a highly conserved RNA recognition motif (RRM) consisting of two subunits, RNP1 and RNP2, which specifically bind to RNAs. Recent studies have revealed that RBM38 regulates the mRNA stability of several tumor-related genes, such as p53 , mdm2 , p63 , p73 , p21 , and c-Myc , by binding to their 3′ untranslated regions (3′ UTRs); thus, RBM38 modulates targeted gene expression and affects the biological processes of tumors. In addition, abnormal RBM38 expression in some malignant tumors and its correlation with prognosis have been documented in many studies, indicating its value for potential clinical applications. In this review, we present an overview of RBM38, specifically highlighting its relationship with tumor manifestation and development. A brief overview of the potential use of RBM38 in cancer therapy is also included to provide ideas for further research on RBM38.

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Midazolam alleviates cellular senescence in SH‐SY5Y neuronal cells in Alzheimer's disease

Wang

Luan

et al. 2022

Brain and Behavior

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Background: Alzheimer's disease (AD) impacts the daily life of aging people. Oligomerized amyloid β (Aβ)-associated neuronal senescence is involved in the pathological mechanism of AD. Blockage of neuronal senescence has been considered an important strategy for the treatment of AD. Midazolam is a hypnotic-sedative drug with pleiotropic properties.Aims: However, the effects of Midazolam in oligomerized Aβ 1.42 -induced neurotoxicity have not been reported previously. Here, we investigate whether Midazolam possesses a beneficial effect against oligomerized Aβ 1.42 in SH-SY5Y neuronal cells. Materials and Methods: Cellular senescence was assessed using senescenceassociated β-galactosidase staining. Telomerase activity was measured using the TeloTAGGG Telomerase PCR ELISA. Results: First, the lactate dehydrogenase release assay demonstrates that 10 and 20 µM are the optimal concentrations of Midazolam used for cell cultures. Senescenceassociated β-galactosidase staining results indicate that exposure to oligomerized Aβ 1.42 significantly increased cellular senescence of SH-SY5Y cells, but it was significantly alleviated by Midazolam. Additionally, Midazolam restored the oligomerized Aβ 1.42 -induced reduction of telomerase activity. Interestingly, we found that oligomerized Aβ 1.42 remarkably reduced human telomerase reverse transcriptase (hTERT) gene expression but increased the telomeric repeat-binding factor 2 (TERF2) expression. However, treatment with Midazolam reversed the effects of oligomerized Aβ 1.42 on the hTERT and TERF2 gene expressions. Importantly, the presence of Midazolam attenuated Aβ 1.42 -induced p53 and p21 expressions. Mechanistically, Midazolam repressed the level of cyclooxygenase-2 (COX-2) and the release of prostaglandin E2. Importantly, overexpression of COX-2 abolished the impact of Midazolam against oligomerized Aβ 1.42 in neuronal senescence. Conclusion:We conclude that the usage of Midazolam is a potential treatment strategy for AD.

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CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication

Cited by 78 publications

References 125 publications

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

RNA-Binding Motif Protein 38 as a Potential Biomarker and Therapeutic Target in Cancer

Midazolam alleviates cellular senescence in SH‐SY5Y neuronal cells in Alzheimer's disease

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