CUL7 promotes cancer cell survival through promoting Caspase‐8 ubiquitination

Kong, Yanjie; Wang, Zehua; Huang, Menghao; Zhou, Zhongmei; Li, Yang; Miao, Huilai; Xing, Wei; Huang, Jian; Mao, Xiaoyun; Chen, Ceshi

doi:10.1002/ijc.32239

Cited by 22 publications

(20 citation statements)

References 49 publications

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“…Kong et al demonstrated that CUL7 promoted the ubiquitination of caspase-8 and inhibited the activation of the death-inducing signaling complex, thereby increasing the survival of cancer cells in a manner mediated by tumor necrosis factor-related apoptosis-induced ligands 28 . This group also revealed that Fbxw8 did not participate in the caspase-8 ubiquitination by CUL7 28 (Fig. 3b ).…”

Section: Cul7 Substrate Proteins In Development and Cancermentioning

confidence: 99%

“…Five cellular proteins have been previously recognized as substrates of the CUL7 E3 ligase: cyclin D1 16 , insulin receptor substrate (IRS-1) 22 , hematopoietic progenitor kinase 1 (HPK1) 23 , Golgi reassembly-stacking protein 65 (GRASP65) 24 , and TBC1 domain family member 31 (TBC1D31) 25 . Recently, additional proteins have been implicated in the degradative process of the CUL7 E3 Ub ligase: histone H2B-like (H2B) 26 , Mof4 family associated protein 1 (MRFAP1) 27 , AID 20 , caspase-8 28 , macrophage stimulating 1 (Mst1) 29 , and pleckstrin homology like domain family B member 2 (LL5β) 30 . Interestingly, several proteins, such as p53 12 , 31 , 32 , SV40 T antigen 33 – 35 , glomulin (GLMN) 36 , PARC 37 , 38 , obscurin-like 1 (OBSL1), and coiled-coil domain containing 8 (CCDC8) 39 , have been shown to interact with CUL7, but this interaction does not affect their stability, suggesting that the CUL7 E3 ligase may perform a proteolytic function and also play a non-proteolytic role.…”

Section: Introduction Of the Cul7 E3 Ligasesmentioning

confidence: 99%

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The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Shi¹,

Du²,

Peng³

et al. 2020

Oncogenesis

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Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.

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Section: Cul7 Substrate Proteins In Development and Cancermentioning

confidence: 99%

Section: Introduction Of the Cul7 E3 Ligasesmentioning

confidence: 99%

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Shi¹,

Du²,

Peng³

et al. 2020

Oncogenesis

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“…Consistent with our current study, CUL7 has been reported to be upregulated and to induce oncogenic functions in multiple cancers. For example, CUL7 promotes the survival of a variety of cancer cells, including MDA-MB-231 breast cancer cells, HeLa cells and HEK293T cells, by promoting caspase-8 ubiquitination [51]. In addition, CUL7 overexpression and unfavourable prognosis have been reported to be correlated in hepatocellular carcinoma [11], epithelial ovarian cancer [12], lung cancer [13], breast cancer [14], and choriocarcinoma [15].…”

Section: Discussionmentioning

confidence: 99%

Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-κB activation

Zhang

Qian

et al. 2020

J Exp Clin Cancer Res

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Background: Cullin-7 (CUL7) is a member of the DOC domain-containing cullin family and is involved in the regulation of cell transformation. However, the clinical significance, potential mechanism and upstream regulators of CUL7 in malignant gliomas remain to be determined. Methods:Expression level data and clinical information were obtained via the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, immunohistochemistry (IHC) and western blot analysis. Gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of CUL7. RNA silencing was performed using siRNA or lentiviral constructs in U87MG and U251 glioma cell lines and GSC267 glioma stem cells. CUL7 overexpression was performed using the GV141-CUL7 plasmid construct. In addition, overexpression of miR-3940-5p was performed and validated by quantitative real-time PCR (qRT-PCR). Cells were characterized in vitro or in vivo to evaluate their molecular status, cell proliferation, invasion, and migration by Cell Counting Kit (CCK)-8, EdU, flow cytometry, colony formation, Transwell and 3D tumour spheroid invasion assays. Coimmunoprecipitation (co-IP) and western blotting were performed to test the mechanisms of activation of the NF-κB signalling pathway.Results: High CUL7 expression was associated with a high tumour grade, a mesenchymal molecular glioma subtype and a poor prognosis in patients. Gene silencing of CUL7 in U87MG and U251 cells significantly inhibited tumour growth, invasion and migration in vitro and in vivo. Western blot analysis revealed that cyclin-dependent kinase inhibitors and epithelial-mesenchymal transition (EMT) molecular markers changed under CUL7 silencing conditions. In contrast, CUL7 overexpression promoted tumour growth, invasion and migration. Gene set enrichment analysis (GSEA) and western blot analysis revealed that CUL7 was positively associated with the NF-κB pathway. Moreover, with coimmunoprecipitation assays, we discovered that CUL7 physically associated with MST1, which further led to ubiquitin-mediated MST1 protein degradation, which promoted activation of the NF-κB signalling pathway. Finally, CUL7 was found to be downregulated by miR-3940-5p, which suppressed the development of gliomas.(Continued on next page)

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“…Cullin-7 has recently been shown to physically interact with caspase-8 [12]. CUL7 prevented the activation of caspase-8 by promoting post-translational modifications of caspase-8 by the addition of non-degradative polyubiquitin chains at the 215th lysine (shown in Figure 2).…”

Section: Negative Regulators Of Trail-mediated Signalingmentioning

confidence: 99%

“…Knockdown of CUL7 re-sensitized cancer cells to TRAIL-triggered apoptotic cell death. Tumor growth was significantly inhibited in mice xenografted with CUL7-silenced MDA-MB-231 cells [12]. CHIP (C terminus HSC70-interacting protein) induced the K6-linked polyubiquitylation of FADD and suppressed the formation of the DISC (Figure 2) [13].…”

Section: Negative Regulators Of Trail-mediated Signalingmentioning

confidence: 99%

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

Shahwar

Iqbal

Nisa³

et al. 2019

IJMS

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Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.

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CUL7 promotes cancer cell survival through promoting Caspase‐8 ubiquitination

Cited by 22 publications

References 49 publications

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-κB activation

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

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