The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53

Zou, Shenshan; Zhu, Y.; Wang, Bin; Qian, Fengyuan; Zhang, Xiang; Wang, Lei; Fu, Chunling; Bao, Hanmo; Xie, Manyi; Gao, Shangfeng; Yu, Rutong; Shi, Hengliang

doi:10.1007/s12035-016-0033-x

Cited by 31 publications

(18 citation statements)

References 35 publications

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“…Among these, ubiquitination was firstly discovered and mostly studied. Besides MDM2, a few other E3 ligases were reported to directly facilitate p53 poly-ubiquitination and degradation, such as COP1 and P300 [28], [29]. However, recently p53 papers discovered a group of E3 ligase or ubiquitin binding proteins, which modulate p53 function in MDM2-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Yang

Wang

et al. 2017

Neoplasia

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The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.

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Section: Discussionmentioning

confidence: 99%

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Yang

Wang

et al. 2017

Neoplasia

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“…The establishment of stable cell lines was performed as we previously described . For stably silencing of TSG101, HepG2 and SMMC‐7721 cells were infected by control and shTSG101#3 viruses, respectively.…”

Section: Methodsmentioning

confidence: 99%

TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10

Liu

Tian

Cao

et al. 2018

J Cellular Molecular Medi

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The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.

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“…Besides the N-terminal RING finger, COP1 has an internal coiled-coil domain and WD40-repeat domains [85,86]. This E3 ligase expresses abundantly in different tissues, including tumor tissues, and contributes to development, cell survival, cell growth, and tumorigenesis [87,88,89,90,91]. COP1 binds to p53 and promotes p53 turnover by targeting it for proteasomal degradation in a ubiquitin-dependent fashion.…”

Section: Constitutive Photomorphogenesis Protein 1 (Cop1) and P53mentioning

confidence: 99%

Essential Roles of E3 Ubiquitin Ligases in p53 Regulation

Sane

Rezvani

2017

IJMS

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The ubiquitination pathway and proteasomal degradation machinery dominantly regulate p53 tumor suppressor protein stability, localization, and functions in both normal and cancerous cells. Selective E3 ubiquitin ligases dominantly regulate protein levels and activities of p53 in a large range of physiological conditions and in response to cellular changes induced by exogenous and endogenous stresses. The regulation of p53’s functions by E3 ubiquitin ligases is a complex process that can lead to positive or negative regulation of p53 protein in a context- and cell type-dependent manner. Accessory proteins bind and modulate E3 ubiquitin ligases, adding yet another layer of regulatory control for p53 and its downstream functions. This review provides a comprehensive understanding of p53 regulation by selective E3 ubiquitin ligases and their potential to be considered as a new class of biomarkers and therapeutic targets in diverse types of cancers.

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The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53

Cited by 31 publications

References 35 publications

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10

Essential Roles of E3 Ubiquitin Ligases in p53 Regulation

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