Mechanisms of p53 Functional De-Regulation: Role of the IκB-α/p53 Complex

Carrà, Giovanna; Crivellaro, Sabrina; Taulli, Riccardo; Guerrasio, Angelo; Saglio, Giuseppe; Morotti, Alessandro

doi:10.3390/ijms17121997

Cited by 10 publications

(11 citation statements)

References 87 publications

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“…It has been reported that p53 regulates the expression of lncRNA when responding to DNA damage . p53, which is known as tumor suppressor, has close association with the progression of many cancers . Several studies demonstrated that p53 inhibited tumor growth by inhibiting cell proliferation .…”

Section: Discussionmentioning

confidence: 99%

Retracted: Long non‐coding RNA reprogramming (lncRNA‐ROR) regulates cell apoptosis and autophagy in chondrocytes

Yang

Tang

et al. 2018

J of Cellular Biochemistry

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Long Non-Coding RNA Reprogramming (lncRNA-ROR) plays an important role in regulating various biologic processes, whereas the effect of lncRNA-ROR in osteoarthritis (OA) is little studied. This study aimed to explore lncRNA-ROR expression in articular cartilage and identify the functional mechanism of lncRNA-ROR in OA. OA cartilage tissues were obtained from 15 OA patients, and 6 normal cartilage tissues were set as controls. Chondrocytes were isolated from the collected cartilage tissues. lncRNA-ROR was knockdown in normal cells and overexpressed in OA cells. Cell viability was determined with Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometric analysis. Moreover, proteins and mRNAs involved in this study were also measured using Western blotting and quantitative real-time PCR (qPCR). Level of lncRNA-ROR was decreased in OA compared with normal chondrocytes, and overexpression of lncRNA-ROR dramatically promoted cell viability of OA chondrocytes. In addition, knockdown lncRNA-ROR inhibited apoptosis and promoted autophagy of normal chondrocytes. Moreover, lncRNA-ROR inhibited the expression of p53 in both mRNA and protein levels. Furthermore, we revealed that lncRNA-ROR regulated apoptosis and autophagy of chondrocytes via HIF1α and p53. The results indicated that lncRNA-ROR played a critical role in the pathogenesis of OA, suggesting that lncRNA-ROR could serve as a new potential therapeutic target for OA.

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Section: Discussionmentioning

confidence: 99%

Retracted: Long non‐coding RNA reprogramming (lncRNA‐ROR) regulates cell apoptosis and autophagy in chondrocytes

Yang

Tang

et al. 2018

J of Cellular Biochemistry

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“…P53, as a well-known tumor suppressor, is involved in tumorigenesis and development of various cancers [ 21 , 22 ]. It can suppress tumor growth and development by attenuating cell proliferation or by activating cell death progression [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Reprogramming (ROR) Promotes Cell Proliferation in Colorectal Cancer via Affecting P53

Jiang

Niu

2017

Med Sci Monit

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BackgroundColorectal cancer (CRC) remains one of the most common lethal malignant tumors worldwide. The correlation between lncRNAs expression and CRC development has not been well identified in the recent literature. This study focused on the role of lncRNA-ROR on CRC progression and development.Material/MethodsQuantitative real-time PCR (qRT-PCR) assay was conducted to identify the expression level of lncRNA-ROR. Cell proliferation and viability were examined by MTT assay and colony formation assay. Cell cycle distribution and apoptosis were detected by flow cytometry. Expressions of p53, p21, and FAS protein levels were assessed by Western blotting. CRC cells transfected with lncRNA-shRNA were injection into nude mice to identify the function of lncRNA-ROR on tumorigenesis in vivo.ResultsThe expression level of lncRNA-ROR was elevated in CRC tissues when compared to adjacent tissues (n=78). lncRNA-ROR knockdown significantly suppressed cell proliferation and viability, while lncRNA-ROR overexpression had the opposite effect. Decreased lncRNA-ROR expression enhanced cell apoptosis and triggered cell cycle arrest in G0/G1 phase, while elevated lncRNA-ROR expression presented the opposite effect. Protein levels of p53 and p53 target genes were affected by lncRNA-ROR in vitro, and downregulation of lncRNA-ROR impeded tumorigenesis in vivo.ConclusionsOur study demonstrates that lncRNA-ROR participates in controlling CRC proliferation, viability, and apoptosis, partially by modulating p53, which provides potential and prospective therapeutic targets for CRC.

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“…However, the real number is probably much higher when the involvement of the entire p53 pathway in tumorigenesis is considered. In tumors in which TP53 is not mutated, p53 itself or its signaling can be inactivated by posttranscriptional and posttranslational modifications, subcellular localization, and interaction with other proteins (10). In tumor cells, a dysfunctional p53 protein often presents an aberrant misfolded and inactive conformation, which accumulates and aggregates to form amyloid-like oligomers and fibrils, related to impairment of p53 roles (11–13).…”

Section: Introductionmentioning

confidence: 99%

Loss of the p53 transactivation domain results in high amyloid aggregation of the Δ40p53 isoform in endometrial carcinoma cells

Santos

Oliveira

Rocha

et al. 2019

Journal of Biological Chemistry

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Dysfunctional p53 formation and activity can result from aberrant expression and subcellular localization of distinct p53 isoforms or aggregates. Endometrial carcinoma (EC) is a cancer type in which p53 status is correlated with prognosis, and TP53 mutations are a frequent genetic modification. Here we aimed to evaluate the expression patterns of different p53 isoforms and their contributions to the formation and subcellular localization of p53 amyloid aggregates in both EC and endometrial nontumor cell lines. We found that full-length (fl) p53 and a truncated p53 isoform, Δ40p53, resulting from alternative splicing of exon 2 or alternative initiation of translation at ATG-40, are the predominantly expressed p53 variants in EC cells. However, Δ40p53 was the major p53 isoform in endometrial nontumor cells. Immunofluorescence assays revealed that Δ40p53 is mainly localized to cytoplasmic punctate structures of EC cells, resembling solid-phase structures similar to those found in neurodegenerative pathologies. Using light-scattering kinetics, CD, and transmission EM, we noted that the p53 N-terminal transactivation domain significantly reduces aggregation of the WT p53 DNA-binding domain, confirming the higher aggregation tendency of Δ40p53, which lacks this domain. This is the first report of cytoplasmic Δ40p53 in EC cells being a major component of amyloid aggregates. The differential aggregation properties of p53 isoforms in EC cells may open up new avenues in the development of therapeutic strategies that preferentially target specific p53 isoforms to prevent p53 amyloid aggregate formation.

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Mechanisms of p53 Functional De-Regulation: Role of the IκB-α/p53 Complex

Cited by 10 publications

References 87 publications

Retracted: Long non‐coding RNA reprogramming (lncRNA‐ROR) regulates cell apoptosis and autophagy in chondrocytes

Retracted: Long non‐coding RNA reprogramming (lncRNA‐ROR) regulates cell apoptosis and autophagy in chondrocytes

Long Non-Coding RNA Reprogramming (ROR) Promotes Cell Proliferation in Colorectal Cancer via Affecting P53

Loss of the p53 transactivation domain results in high amyloid aggregation of the Δ40p53 isoform in endometrial carcinoma cells

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