UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain

Wang, Yangyang; Yan, Xinke; Zeng, Su; Zhang, Ting; Cheng, Fengjuan; Chen, Rongjuan; Duan, Changzhu

doi:10.1007/s10529-018-2577-5

Cited by 10 publications

(8 citation statements)

References 15 publications

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“…Through cooperative DNA and histone binding, it may contribute to tighter epigenetic control of the gene expression in differentiated cells. Recent research found that UHRF2 can promote the DNA damage response (Wang et al, 2018). The gene DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate the molecular chaperone activity by stimulating the ATPase activity.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA as a Potential Biomarker for Forensic Age Prediction

Wang

Wei

et al. 2022

Front. Genet.

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In forensic science, accurate estimation of the age of a victim or suspect can facilitate the investigators to narrow a search and aid in solving a crime. Aging is a complex process associated with various molecular regulations on DNA or RNA levels. Recent studies have shown that circular RNAs (circRNAs) upregulate globally during aging in multiple organisms such as mice and C.elegans because of their ability to resist degradation by exoribonucleases. In the current study, we attempted to investigate circRNAs’ potential capability of age prediction. Here, we identified more than 40,000 circRNAs in the blood of thirteen Chinese unrelated healthy individuals with ages of 20–62 years according to their circRNA-seq profiles. Three methods were applied to select age-related circRNA candidates including the false discovery rate, lasso regression, and support vector machine. The analysis uncovered a strong bias for circRNA upregulation during aging in human blood. A total of 28 circRNAs were chosen for further validation in 30 healthy unrelated subjects by RT-qPCR, and finally, 5 age-related circRNAs were chosen for final age prediction models using 100 samples of 19–73 years old. Several different algorithms including multivariate linear regression (MLR), regression tree, bagging regression, random forest regression (RFR), and support vector regression (SVR) were compared based on root mean square error (RMSE) and mean average error (MAE) values. Among five modeling methods, regression tree and RFR performed better than the others with MAE values of 8.767 years (S.rho = 0.6983) and 9.126 years (S.rho = 0.660), respectively. Sex effect analysis showed age prediction models significantly yielded smaller prediction MAE values for males than females (MAE = 6.133 years for males, while 10.923 years for females in the regression tree model). In the current study, we first used circRNAs as additional novel age-related biomarkers for developing forensic age estimation models. We propose that the use of circRNAs to obtain additional clues for forensic investigations and serve as aging indicators for age prediction would become a promising field of interest.

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Section: Discussionmentioning

confidence: 99%

Circular RNA as a Potential Biomarker for Forensic Age Prediction

Wang

Wei

et al. 2022

Front. Genet.

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“…In addition to the above four E3 ubiquitin ligases, other proteins can regulate the degradation process of p21. For example, five E3 ubiquitin ligases (UHRF2 [ 33 ], UBR5 [ 34 ], SOCS1 [ 35 ], COPA3 [ 36 ] and ZNF313 [ 26 , 37 ]) and two deubiquitylases (USP11 [ 38 ] and USP36 [ 39 ]) have been reported to mediate p21 stability. In our work, we investigated four most frequently E3 ligases, especially SKP2.…”

Section: Discussionmentioning

confidence: 99%

HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21 via the MAPK/ERK1/2 and AKT/GSK3β signaling pathways

Chen

Huang

Zhou

et al. 2018

J Exp Clin Cancer Res

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BackgroundHolliday junction recognition protein (HJURP) has been implicated in many cancers including hepatocellular carcinoma (HCC). However, the underlying mechanism by which HJURP promotes HCC cell proliferation remains unclear.MethodsRT-qPCR and immunohistochemistry were used to detect HJURP expression in HCC and adjacent tumor tissues and HCC cell lines. The localization of p21 were determined by immunofluorescence and western blot. Co-immunoprecipitation and western blot were used to validate the p21 stability and signaling pathways affected by HJURP. The effects of HJURP on HCC cell proliferation were assessed both in vivo and in vitro. The ERK1/2 pathway inhibitor U0126 and AKT pathway agonist SC-79 were used to treat HCC cell lines for further mechanistic investigations.ResultsHJURP expression was higher in HCC tissues than in para-tumor tissues. Moreover, ectopic HJURP expression facilitated the proliferation of HCC cells, whereas the depletion of HJURP resulted in decreased cell growth in vitro and in vivo. Furthermore, the effects of HJURP silencing were reversed by p21 knockdown. Likewise, p21 overexpression inhibited cell growth ability mediated by HJURP elevation. Mechanistically, HJURP destabilized p21 via the MAPK/ERK1/2 and AKT/GSK3β pathways, which regulated the nucleus-cytoplasm translocation and ubiquitin-mediated degradation of p21. Clinically, high HJURP expression was correlated with unfavorable prognoses in HCC individuals.ConclusionsOur data revealed that HJURP is an oncogene that drives cell cycle progression upstream of p21 in HCC. These findings may provide a potential therapeutic and prognostic target for HCC.

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“…However, the degradation of p21 mediated by human CRL2 LRR1 complex does not appreciably affect cell cycle progression [ 190 ]. Up to date, ZNF313 [ 191 ], RNF126 [ 192 ], CHIP [ 193 ], CRL4B DCAF11 [ 194 ], UHRF2 [ 195 ], SPSB1 [ 196 ], NEDD4 [ 197 ], and FBXO22 [ 198 ] have also been added to the growing list of E3 ubiquitin ligases that control the abundance of p21 protein. Compared with the ubiquitination studies of p21, the identified deubiquitinases targeting p21 are much less.…”

Section: Ubiquitination and Deubiquitination Involved In Ckismentioning

confidence: 99%

The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression

Zou

Lin

2021

IJMS

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The cell cycle is a collection of events by which cellular components such as genetic materials and cytoplasmic components are accurately divided into two daughter cells. The cell-cycle transition is primarily driven by the activation of cyclin-dependent kinases (CDKs), the activities of which are regulated by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors (CKIs). Thus, the ubiquitin-proteasome system (UPS) plays a pivotal role in the regulation of the cell-cycle process via recognition, interaction, and ubiquitination or deubiquitination of key proteins. The illegitimate degradation of tumor suppressor proteins and oncoproteins or, inversely, abnormally high accumulation results in cell proliferation deregulation, genomic instability, and cancer occurrence. In this review, we demonstrate the diversity and complexity of the UPS machinery regulation of the cell cycle. A profound understanding of the ubiquitination machinery will provide new insights into the regulation of the cell-cycle transition, cancer treatment, and the development of anti-cancer drugs.

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UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain

Abstract: UHRF2 may negatively modulate p21 to regulate DNA damage response, suggesting a novel pathway of UHRF2 repairing DNA damage through the partial regulation of p21.

Cited by 10 publications

References 15 publications

Circular RNA as a Potential Biomarker for Forensic Age Prediction

Circular RNA as a Potential Biomarker for Forensic Age Prediction

HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21 via the MAPK/ERK1/2 and AKT/GSK3β signaling pathways

The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression

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