Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-κB and β-catenin/TCF signaling pathways

Wang, Lina; Feng, Wenli; Yang, Xiao; Yang, Feifei; Wang, Rong; Ren, Qian; Zhu, Xiaofan; Zheng, Guoguang

doi:10.1038/s41419-018-0440-1

Cited by 45 publications

(37 citation statements)

References 48 publications

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“…Consistently, β-TrCP2 depletion inhibits the proliferation of MEFs [33]. Conversely, β-TrCP2 overexpression accelerates lymphocytic leukemia cell proliferation in vitro and tumorigenesis in vivo [39]. Therefore, targeted inactivation of β-TrCP2 possessing oncogenic properties might be a promising anticancer therapy strategy.…”

Section: Discussionmentioning

confidence: 90%

The cross talk of two family members of β-TrCP in the regulation of cell autophagy and growth

et al. 2019

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β-transducin repeat-containing protein (β-TrCP), one of the best-characterized substrate recognition components of the SKP1-CUL1-F-box (SCF) E3 ligase, has two distinct paralogs, β-TrCP1 and β-TrCP2, expressed in mammals. Through governing the ubiquitination and degradation of numerous key regulators, β-TrCP1/2 regulates various cellular physiological and pathological processes. However, whether and how these two proteins cross talk and whether they regulate cell autophagy and proliferation in different manners is completely unknown. Herein, we report that β-TrCP1 and β-TrCP2 are the physiological substrates of SCF E3 ligase and target each other for degradation that is dependent on their β-TrCP degron sequences. Furthermore, glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1. Finally, we found that β-TrCP2, not β-TrCP1, preferentially degrades DEPTOR and REDD1, the inhibitors of mTORC1, to activate mTORC1, leading to autophagy inhibition and cell growth. Thus, our study demonstrates that β-TrCP1 and β-TrCP2 mutually target each other for degradation and that β-TrCP2 acts as a dominant paralog in the regulation of cell autophagy and growth, which might be a promising anticancer target.

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Section: Discussionmentioning

confidence: 90%

The cross talk of two family members of β-TrCP in the regulation of cell autophagy and growth

et al. 2019

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“…To date, no study has reported the effect of the interaction of CUL7 and Fbxw11 in cancer. Wang et al revealed that the Fbxw11 protein level was aberrantly upregulated in patients with lymphocytic leukemia, and the effects were mediated by the stimulation of cell-cycle progression and activation of the NF-κB and β-catenin/TCF signaling pathways rather than the induction of apoptosis 93 . Moreover, the Fbxw11 protein level is increased in mouse skin tumors and promotes cell growth 94 , migration, and invasion 95 through activation of the NF-κB signaling pathway.…”

Section: The Ring Box Protein Rbx1 Adaptor Skp1 and F-box Proteins mentioning

confidence: 99%

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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“…NF-κB and β-catenin/TCF play important roles in CC progression [23, 24]. Since FBXW11 could activate both the NF-κB and β-catenin/TCF signaling pathways [25], we suspected that lncRNA PCGEM1 may regulate these two signaling pathways through FBXW11. For confirmation, a dual luciferase reporter system was used and the results showed that both the NF-κB and β-catenin/TCF signaling pathways were enhanced by PCGEM1 overexpression, while knockdown of FBXW11 abolished this upregulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

The long noncoding RNA PCGEM1 promotes cell proliferation, migration and invasion via targeting the miR-182/FBXW11 axis in cervical cancer

2019

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Background: Cervical cancer (CC) is the fourth leading cause of cancer-associated death in women worldwide. Recently, long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to involve in the initiation and progression of human cancers. However, to date, the clinical and functional significance of PCGEM1 expression in CC progression remains unknown. Methods: qRT-PCR was performed to investigate PCGEM1 expression levels in CC tissues and cell lines. The effect of PCGEM1 on CC cells was assessed by gain-and loss-of-function assays. MS2-binding sequences-MS2-binding proteinbased RIP assay (MS2-RIP), RNA pull-down and Luciferase reporter assays were performed to investigate the interaction between PCGEM1 and miR-182. The association between miR-182 and F-box and WD repeat domain containing 11 (FBXW11) was verified by luciferase reporter assay. The effect of PCGEM1 on the NF-κB and β-catenin/TCF signaling pathways was determined by luciferase reporter assay. Results: Our present study showed that PCGEM1 was significantly upregulated in CC tissues and cell lines. Overexpression of PCGEM1 was correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node, distant metastasis and poor prognosis in CC patients. Functionally, PCGEM1 promoted cell proliferation, cell cycle progression, migration and invasion, while suppressed cell apoptosis in CC cells. Further mechanistic investigation revealed that PCGEM1 associated with miR-182 and suppressed its expression. PCGEM1 could act as a competing endogenous (ceRNA) of oncogene F-box and WD repeat domain containing 11 (FBXW11) for miR-182 in CC cells. Additionally, PCGEM1 was capable to activate the NF-κB and β-catenin/TCF signaling pathways, which was reversed by inhibition of FBXW11. Conclusion: In conclusion, our findings demonstrated that PCGEM1-miR-182-FBXW11 axis play an important role in CC progression, and indicated a promising therapeutic target for CC patients.

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Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-κB and β-catenin/TCF signaling pathways

Cited by 45 publications

References 48 publications

The cross talk of two family members of β-TrCP in the regulation of cell autophagy and growth

The cross talk of two family members of β-TrCP in the regulation of cell autophagy and growth

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

The long noncoding RNA PCGEM1 promotes cell proliferation, migration and invasion via targeting the miR-182/FBXW11 axis in cervical cancer

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