Involvement of the p53/p21 complex in p53-dependent gene expression

Kim, Ukjin; Kim, Kwang Seok; Park, Jongkuk; Um, Hong‐Duck

doi:10.1016/j.bbrc.2022.07.022

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…Since many p53 transcriptional downstream genes, such as p21 , can regulate cell growth, 34 we hypothesize that the decreased p53 transcriptional activity upon NEDDylation can induce cancer cell growth. The cell counting data showed that overexpression of UBE1C and NEDD8 in A549 and H460 lung cancer cells increased the cell proliferation rate (Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

“…[27][28][29][30] p53 protein is composed of four functional domains and serves as an important transcriptional factor for many genes. [31][32][33][34][35] In response to cellular stresses, multiple lysine residues on the C-terminal regulatory domain could be modified by various PTMs, including phosphorylation, ubiquitination, sumoylation, NEDDylation, and acetylation. [36][37][38][39] For example, the K370, K372, and K373 of p53 C-terminal domain are the main sites for NEDD8 conjugation, regulated by MDM2 and FBXO11 through their activity as ubiquitin E3 ligases.…”

Section: Introductionmentioning

confidence: 99%

“…p53 protein is composed of four functional domains and serves as an important transcriptional factor for many genes 31–35 . In response to cellular stresses, multiple lysine residues on the C‐terminal regulatory domain could be modified by various PTMs, including phosphorylation, ubiquitination, sumoylation, NEDDylation, and acetylation 36–39 .…”

Section: Introductionmentioning

confidence: 99%

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UBE1C is upregulated and promotes neddylation of p53 in lung cancer

Liu,

Shih,

Wang

et al. 2023

The FASEB Journal

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NEDDylation is a type of protein post‐translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C‐mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C‐mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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UBE1C is upregulated and promotes neddylation of p53 in lung cancer

Liu,

Shih,

Wang

et al. 2023

The FASEB Journal

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“…P21 is not only a downstream target of p53, but also binds directly to p53 to form the p53/P21 complex. This complex binds to Bcl-2 family proteins to promote the expression of Bax [ 87 ]. Furthermore, in addition to the direct activation of p53 signalling, an indirect activation pathway exists for 6-shogaol.…”

Section: The Regulation Of 6-shogaol On Cancer Related Signal Pathwaysmentioning

confidence: 99%

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system

Jia,

Li,

Meng

et al. 2023

Chin Med

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Cancer is a malignant disease that has plagued human beings all the time, but the treatment effect of commonly used anticancer drugs in clinical practice is not ideal by reason of their drug tolerance and Strong adverse reactions to patients. Therefore, it is imperative to find effective and low-toxic anticancer drugs. Many research works have shown that natural products in Chinese herbal medicine have great anticancer potential, such as 6-shogaol, a monomer composition obtained from Chinese herbal ginger, which has been confirmed by numerous in vitro or vivo studies to be an excellent anti-cancer active substance. In addition, most notably, 6-shogaol has different selectivity for normal and cancer cells during treatment, which makes it valuable for further research and clinical development. Therefore, this review focus on the anti-cancer attributes, the mechanism and the regulation of related signaling pathways of 6-shogaol. In addition, its synergy with commonly used anticancer drugs, potential drug delivery systems and prospects for future research are discussed. This is the first review to comprehensively summarize the anti-cancer mechanism of 6-shogaol, hoping to provide a theoretical basis and guiding significance for future anti-cancer research and clinical development of 6-shogaol. Graphical Abstract

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“…Thus, P21 may be an essential p53 growth suppression pathway component. Some findings indicate that the p53/p21 complex regulates cell apoptosis by targeting Bcl-2 proteins ( Kim et al, 2022 ). P21 protein, a cyclin-dependent kinase inhibitor (CKI), can bind to and inhibit the activity of CDK1, CDK2, and CDK4/6 enzyme complexes ( Marchetti et al, 1996 ), thereby acting as a cell cycle regulator at the G1 and S phases ( Kikuchi et al, 2022 ).…”

Section: Effects and Mechanisms Of Nps On Apoptosis In Ecmentioning

confidence: 99%

Natural products modulate cell apoptosis: a promising way for treating endometrial cancer

et al. 2023

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Endometrial cancer (EC) is a prevalent epithelial malignancy in the uterine corpus’s endometrium and myometrium. Regulating apoptosis of endometrial cancer cells has been a promising approach for treating EC. Recent in-vitro and in-vivo studies show that numerous extracts and monomers from natural products have pro-apoptotic properties in EC. Therefore, we have reviewed the current studies regarding natural products in modulating the apoptosis of EC cells and summarized their potential mechanisms. The potential signaling pathways include the mitochondria-dependent apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, the mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, NF-κB-mediated apoptotic pathway, PI3K/AKT/mTOR mediated apoptotic pathway, the p21-mediated apoptotic pathway, and other reported pathways. This review focuses on the importance of natural products in treating EC and provides a foundation for developing natural products-based anti-EC agents.

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Involvement of the p53/p21 complex in p53-dependent gene expression

Cited by 8 publications

References 15 publications

UBE1C is upregulated and promotes neddylation of p53 in lung cancer

UBE1C is upregulated and promotes neddylation of p53 in lung cancer

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system

Natural products modulate cell apoptosis: a promising way for treating endometrial cancer

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