p53-mediated G1 arrest requires the induction of both p21 and Killin in human colon cancer cells

Luo, Di; Yu, Chunhua; Yu, Jian; Su, Chao; Li, Shun; Peng, Liang

doi:10.1080/15384101.2021.2014249

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…These changes disable cyclin B1/CDK1, which is responsible for M phase entry, resulting in G2 arrest until the DNA damage is repaired 43 . p21, a target of the p53 transcription factor, is activated during cellular stress or DNA damage; p53 also participates in the initiation of cell death when DNA damage levels cannot be sufficiently reduced 44 . Previous studies have shown that NEK2 activation in response to DNA damage delays mitotic entry 45 .…”

Section: Discussionmentioning

confidence: 99%

“… 43 p21, a target of the p53 transcription factor, is activated during cellular stress or DNA damage; p53 also participates in the initiation of cell death when DNA damage levels cannot be sufficiently reduced. 44 Previous studies have shown that NEK2 activation in response to DNA damage delays mitotic entry. 45 Our results indicate that NEK2 inhibition‐induced DNA damage activates the ATM‐p53‐p21 pathway and increases CHEK1 and CHEK2 levels, ultimately leading to G2 arrest.…”

Section: Discussionmentioning

confidence: 99%

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NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β‐catenin signalling pathway

Jeon,

Jeong,

Kang

et al. 2024

Cell Proliferation

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NIMA‐related kinase 2 (NEK2) is a serine/threonine protein kinase that regulates mitosis and plays pivotal roles in cell cycle regulation and DNA damage repair. However, its function in porcine embryonic development is unknown. In this study, we used an NEK2‐specific inhibitor, JH295 (JH), to investigate the role of NEK2 in embryonic development and the underlying regulatory mechanisms. Inhibition of NEK2 after parthenogenesis activation or in vitro fertilization significantly reduced the rates of cleavage and blastocyst formation, the numbers of trophectoderm and total cells and the cellular survival rate compared with the control condition. NEK2 inhibition delayed cell cycle progression at all stages from interphase to cytokinesis during the first mitotic division; it caused abnormal nuclear morphology in two‐ and four‐cell stage embryos. Additionally, NEK2 inhibition significantly increased DNA damage and apoptosis, and it altered the expression levels of DNA damage repair‐ and apoptosis‐related genes. Intriguingly, NEK2 inhibition downregulated the expression of β‐catenin and its downstream target genes. To validate the relationship between Wnt/β‐catenin signalling and NEK2 during porcine embryonic development, we cultured porcine embryos in JH‐treated medium with or without CHIR99021, a Wnt activator. CHIR99021 co‐treatment strongly restored the developmental parameters reduced by NEK2 inhibition to control levels. Our findings suggest that NEK2 plays an essential role in porcine embryonic development by regulating DNA damage repair and normal mitotic division via the Wnt/β‐catenin signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β‐catenin signalling pathway

Jeon,

Jeong,

Kang

et al. 2024

Cell Proliferation

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“…HEK-293T cell and human colon cancer cell line HCT116 (p53 WT) were obtained from the American Type Culture Collection (ATCC). HCT116 (p53 Null) cell was generated by using CRISPR/Cas9, and donated as a kind gift from Dr. Dan Luo 13 . HEK-293T cells were maintained in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% fetal bovine serum (PAN, Germany), 100 U/mL penicillin and 100 µg/mL streptomycin (GIBCO, Rockville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

ER stress activates TAp73α to promote colon cancer cell apoptosis via the PERK-ATF4 pathway

Sun¹,

Yao²,

Xiao³

et al. 2023

J. Cancer

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Colorectal cancer (CRC) is the fourth most diagnosed cancer worldwide. 43% of CRCs harbor p53 mutations. The tumor suppressor p53 induces cell growth arrest and/or apoptosis in response to stress, including endoplasmic reticulum (ER) stress. It has been documented that the p53 gene is mutated in more than 50% of human tumors and loses its tumor suppressor function, suggesting that ER stress-induced apoptosis might not rely on p53. In this study, we found that activation of ER stress promotes p53 null colon cancer cell apoptosis concomitant with an increased level of the TAp73α protein, a homologue of p53 in vitro and in vivo . Knockdown of TAp73α partially restores ER stress-induced apoptosis, indicating that ER stress stimulates apoptosis in a manner dependent on TAp73α, but not p53. Furthermore, we found that ER stress activates TAp73α mRNA and protein expression through PERK signalling, a branch of the unfolded protein response (UPR). Moreover, PERK promotes TAp73α expression by upregulating the expression of the transcription factor ATF4. ATF4 directly activates the transcription of TAp73α. Consistent with this finding, ATF4 knockdown inhibited PERK- or ER stress-induced TAp73α expression. Our findings reveal that ER stress activates TAp73α to promote colon cancer cell apoptosis via the PERK-ATF4 signalling. Therefore, prolonged ER stress or upregulation of TAp73α might be a therapeutic strategy for colon cancer.

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“…The induction of the p53-dependent mode of apoptosis was observed in HCT116 cells (as evidenced by phosphatidylserine exposure on the outer surface of the cell membrane and activation of caspase-3), whereas in U-251 cells, autophagy prevailed (as evidenced by accumulation of the LC3 protein and increased expression of the LC3 and p62 genes). Upon looking more deeply into apoptosis induction in HCT116 cells, a reduction in the levels of the p21/CDKN1A protein, which is the key player in p53-mediated cell cycle arrest triggered by DNA damage and is thought to be involved in the cellular response to oxidative stress, , was observed. In U-251 cells, an increase in the expression of Beclin-1, which participates in autophagy initiation, was detected.…”

Section: Mechanisms Of Biological Activity Of Ionic Liquids: State Of...mentioning

confidence: 99%

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

Egorova,

Kibardin,

Posvyatenko

et al. 2024

Chem. Rev.

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The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.

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p53-mediated G1 arrest requires the induction of both p21 and Killin in human colon cancer cells

Cited by 8 publications

References 31 publications

NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β‐catenin signalling pathway

NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/β‐catenin signalling pathway

ER stress activates TAp73α to promote colon cancer cell apoptosis via the PERK-ATF4 pathway

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

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