3F‑Box protein 32 degrades ataxia telangiectasia and Rad3‑related and regulates DNA damage response induced by gemcitabine in pancreatic cancer

Yang, Chong; Fan, Ping; Zhu, Shaihong; Yang, Hongji; Jin, Xin; Wu, Heshui

doi:10.3892/ol.2018.8367

Cited by 5 publications

(8 citation statements)

References 29 publications

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“…However, ATR mRNA was increased immediately after irradiation, which indicated the presence of degradation of ATR protein after 24 h irradiation. Yang et al reported that FBXO32 acts as a ubiquitin E3 ligase, which targets to ATR protein and leads to protein degradation in pancreatic cancer (19). In the data of Kansara et al(GSE50532), we found a decrease in FBXO32 mRNA expression within 4 to 16 hours after irradiation, but the expression rose rapidly after 24 h irradiation (31).…”

Section: Discussionsupporting

confidence: 43%

“…In this study, we conformed that FBXO32 can bind ATR to induce its ubiquitination degradation in OS cells. Furthermore, FBXO32 has been also reported to be involved in multiple tumorigenesis and tumor progression (19,32,33). Taken together, we mainly illustrated a mechanism of FBXO32/ATR/ATM/EXO1 axis mediating radiotherapy resistance.…”

Section: Discussionmentioning

confidence: 54%

“…FBXO32 (MAFbx/Atrogin-1) is an E3 ubiquitin ligase, which was reported to be able to degrade c-Myc protein in HCT116 cells (18). Yang et al reported that FBXO32 are also involved in DNA damage repair in pancreatic cancer (19). However, its role in OS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Yang et al . [19] reported that FBXO32 is also involved in DNA damage repair in pancreatic cancer. However, its role in OS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Lu¹,

Huang²,

Li³

et al. 2023

ABBS

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Background: Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents.In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens signi cantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches as they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remains unclear. This study aimed to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Methods: Bioinformaticsmethods were employed to analyze differential gene expression and the correlations with prognosis in OS. Cell counting kit 8 assays, clone formation assays, and ow cytometry were used to evaluate cell survivaland apopotosisunder IR. Co-IP assays detected protein-protein interactions. Results: Bioinformatics analysis revealed that EXO1 is closely related to the survival, apoptosis and poorer prognosis in OS. The silencingof EXO1 suppressed cell proliferation and increased the sensitivity of OS cells. Molecular biological experiments showed that the ATMand ATR acted as the switch to regulate EXO1 expression under IR. Conclusion: Higher expression of EXO1, which was closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated-ATM enhanced the expression of EXO1, and phosphorylated-ATR induced the degradation of EXO1. More importantly, FBXO32 degraded ATR via ubiquitination in time dependent. Our data may provide a reference for future research on mechanisms, clinical diagnosis, and treatment of OS.

show abstract

Section: Discussionsupporting

confidence: 43%

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

“…Yang et al . [19] reported that FBXO32 is also involved in DNA damage repair in pancreatic cancer. However, its role in OS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Lu¹,

Huang²,

Li³

et al. 2023

ABBS

View full text Add to dashboard Cite

show abstract

“…FBXO32 (MAFbx/Atrogin-1) is an E3 ubiquitin ligase, which was reported to be able to degrade c-Myc protein in HCT116 cells [18]. Yang et al reported that FBXO32 are also involved in DNA damage repair in pancreatic cancer [19]. However, its role in OS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Huang

et al. 2022

Preprint

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Background: Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens significantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches as they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remains unclear. This study aimed to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Methods: Bioinformatics methods were employed to analyze differential gene expression and the correlations with prognosis in OS. Cell counting kit 8 assays, clone formation assays, and flow cytometry were used to evaluate cell survival and apopotosis under IR. Co-IP assays detected protein-protein interactions. Results: Bioinformatics analysis revealed that EXO1 is closely related to the survival, apoptosis and poorer prognosis in OS. The silencing of EXO1 suppressed cell proliferation and increased the sensitivity of OS cells. Molecular biological experiments showed that the ATM and ATR acted as the switch to regulate EXO1 expression under IR. Conclusion: Higher expression of EXO1, which was closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated-ATM enhanced the expression of EXO1, and phosphorylated-ATR induced the degradation of EXO1. More importantly, FBXO32 degraded ATR via ubiquitination in time dependent. Our data may provide a reference for future research on mechanisms, clinical diagnosis, and treatment of OS.

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Impact of posttranslational modifications in pancreatic carcinogenesis and treatments

Chen

Zheng

Wan

et al. 2021

Cancer Metastasis Rev

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3F‑Box protein 32 degrades ataxia telangiectasia and Rad3‑related and regulates DNA damage response induced by gemcitabine in pancreatic cancer

Cited by 5 publications

References 29 publications

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Impact of posttranslational modifications in pancreatic carcinogenesis and treatments

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