pVHL mediates K63-linked ubiquitination of IKKβ, leading to IKKβ inactivation

Wang, Yuxin; Zhao, Wenting; Gao, Qiang; Фан, Ли; Qin, Yanqing; Zhou, Hu; Li, Min; Fang, Jing

doi:10.1016/j.canlet.2016.09.009

Cited by 16 publications

(16 citation statements)

References 35 publications

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“… 70 The IKKβ subunit is also polyubiquitinated by a K63-linked chain in human cervical HeLa cells. 79 Importantly, activation of IKK is essential to productive signaling and NFκB-mediated transcription, and its activation depends on the binding of Met1-Ub by the IKK subunit NEMO. 80 …”

Section: Posttranslational Modifications Of Nfκb Proteinsmentioning

confidence: 99%

Role of the NFκB-signaling pathway in cancer

Xia¹,

Tan²,

Zhou³

et al. 2018

OTT

345

218

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Cancer is a group of cells that malignantly grow and proliferate uncontrollably. At present, treatment modes for cancer mainly comprise surgery, chemotherapy, radiotherapy, molecularly targeted therapy, gene therapy, and immunotherapy. However, the curative effects of these treatments have been limited thus far by specific characteristics of tumors. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. Targeted therapies against effectors in oncogenic signaling have improved the outcomes of cancer patients. NFκB is an important signaling pathway involved in pathogenesis and treatment of cancers. Excessive activation of the NFκB-signaling pathway has been documented in various tumor tissues, and studies on this signaling pathway for targeted cancer therapy have become a hot topic. In this review, we update current understanding of the NFκB-signaling pathway in cancer.

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Section: Posttranslational Modifications Of Nfκb Proteinsmentioning

confidence: 99%

Role of the NFκB-signaling pathway in cancer

Xia¹,

Tan²,

Zhou³

et al. 2018

OTT

345

218

View full text Add to dashboard Cite

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“…The activation of NF-κB in chronic hypoxia occurs in many ways. In particular, under the hypoxia condition inhibitor of NF-κB kinase (IKK) activity increases by reducing the hydroxylation of IKKβ by PHD1 [106,107]. There is also an increase in Ca 2+ in the cytoplasm, which results in the activation of calcium/calmodulin-dependent kinase 2 (CaMK2) and in consequence, the ubiquitination of IKKγ/NF-κB essential modulator (NEMO) [108].…”

Section: Chronic Hypoxiamentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

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“…Wang and colleagues demonstrated that pVHL mediates the K63-ubiquitination of IKKβ. Surprisingly, this modification does not lead to degradation, but prevents TAK1-IKKβ interaction, and consequent IKKβ phosphorylation and NF-κB activation [193]. Considering this novel function of pVHL regulating the NF-κB pathway, new therapeutic possibilities might be speculated, especially to inhibit the aberrant activation of the NF-κB pathway in some neoplastic contexts.…”

Section: Future Prospective In Cancer Therapeutics: Targeting Hif mentioning

confidence: 99%

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

2017

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Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk.

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pVHL mediates K63-linked ubiquitination of IKKβ, leading to IKKβ inactivation

Cited by 16 publications

References 35 publications

Role of the NFκB-signaling pathway in cancer

Role of the NFκB-signaling pathway in cancer

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

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pVHL mediates K63-linked ubiquitination of IKKβ, leading to IKKβ inactivation

Cited by 16 publications

References 35 publications

Role of the NF&kappa;B-signaling pathway in cancer

Role of the NF&kappa;B-signaling pathway in cancer

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

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Product

Resources

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Role of the NFκB-signaling pathway in cancer

Role of the NFκB-signaling pathway in cancer