Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-κB pathway

Jin, Hong; Jin, Xuejun; Lee, Jun Young

doi:10.1016/j.bbrc.2010.08.107

Cited by 20 publications

(16 citation statements)

References 22 publications

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“…Therefore, identification of the genes and their products that lead to tumorigenesis is critical for providing new diagnostic and prognostic methods and potential therapeutic targets. Previously, it has been reported that ZFP91 is an important oncoprotein that is associated with the proliferation and tumorigenesis of many human cancer cells [3–6, 27]. Importantly, ZFP91 stabilizes and activates NIK, a crucial kinase for the non-canonical NF-κB pathway, which is associated with cancer growth and survival.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ZFP91 plays a critical role in acute myelogenous leukemia and prostate pathology [3, 4]. Our previous study indicated that ZFP91 is an atypical E3 ligase activating NF-κB-inducing kinase (NIK) via Lys 63 -linked ubiquitination in the noncanonical NF-κB signaling pathway [5, 6]. However, the underlying mechanism of ZFP91 in tumorigenesis has not been well defined.…”

Section: Introductionmentioning

confidence: 99%

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Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

Wang

et al. 2016

Oncotarget

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Zinc finger protein 91 (ZFP91) has been reported to be involved in various biological processes. However, the clinical significance and biological role of ZFP91 in colon cancer remains unknown. Here, we show that ZFP91 expression is upregulated in patients with colon cancer. We found that ZFP91 upregulated HIF-1α at the levels of promoter and protein in colon cancer cells. Using chromatin immunoprecipitation, electrophoretic mobility shift assay and luciferase reporter gene assay, we found that NF-κB/p65 is required for the binding of ZFP91 to the HIF-1α promoter at −197/−188 base pairs and for the transcriptional activation of HIF-1α gene mediated by ZFP91. Flow cytometry, 5-ethynyl-2′-deoxyuridine (EdU) incorporation and tumor xenograft assay demonstrated that ZFP91 enhanced cell proliferation of colon cancer through upregulating HIF-1α in vitro and in vivo. Furthermore, ZFP91 is positively associated with HIF-1α in human colon cancer. Thus, we concluded that ZFP91 activates transcriptional coregulatory protein HIF-1α through transcription factor NF-κB/p65 in the promotion of proliferation and tumorigenesis in colon cancer cell. ZFP91 may serve as a driver gene to activate HIF-1α transcription in the development of cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

Wang

et al. 2016

Oncotarget

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“…Functions of this additional and more specific NF- κ B activation pathway are not thoroughly studied; however available data suggest its involvement in prostate cancer biology [10, 27]. In vitro stimulation of cancer cells with TNF and LIGHT (peptide activating both canonical and alternative NF- κ B signaling pathway) stimulates ZFP91 expression (in MCF-7 cells for TNF and HeLa cells for LIGHT) in a dose dependant manner [6, 8]. TNF influence on growth and function of prostate cancer cells in vitro has been well documented and, among other things, it is proven to induce apoptosis in LNCaP cells [32].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that ZFP91 protein functions as an atypical E3 ubiquitin-protein ligase. Ubiquitination of NIK by ZFP91 leads to its stabilization and activation of the noncanonical NF- κ B pathway and this pathway's target genes expression [7, 8]. What is important, available data imply oncogenic activity of the NIK and its overexpression has been associated with cancer pathogenesis in, for example, melanoma, pancreatic, breast, and lung cancer [11].…”

Section: Introductionmentioning

confidence: 99%

ZFP91: A Noncanonical NF-κB Signaling Pathway Regulator with Oncogenic Properties Is Overexpressed in Prostate Cancer

Paschke

Jopek

Szyszka

et al. 2016

BioMed Research International

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Novel molecular targets are being searched to aid in prostate cancer diagnosis and therapy. Recently, ZFP91 zinc finger protein has been found to be upregulated in prostate cancer cell lines. It is a potentially important oncogenic protein; however only limited data regarding its biological function and expression patterns are available. To date, ZFP91 has been shown to be a key factor in activation of noncanonical NF-κB signaling pathway as well as to be involved in HIF-1α signaling in cancer cells. The present study aimed to characterize ZFP91 expression in prostate cancer specimens. Furthermore, since our earlier reports showed discrepancies between ZFP91 mRNA and protein levels, we studied this interrelationship in LNCaP and PC-3 prostate cancer cell lines using siRNA mediated knockdown. QPCR analysis revealed marked upregulation of ZFP91 mRNA in the majority of prostate cancer specimens. Transfection of prostate cancer cells with ZFP91 siRNA resulted in a 10-fold decrease in mRNA levels. On a protein level, however, no inhibitory effect was observed over the time of the cell culture. We conclude that ZFP91 is overexpressed in prostate cancer and that potential accumulation of the ZFP91 protein in studied cells may be of importance in prostate cancer biology.

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“…ZFP91 is an E3 ubiquitin ligase that has the ability to bind directly to NIK, promoting its stabilization and downstream non-canonical signaling (Figure 3). ZFP91 is also essential in CD40-mediated NIK activation in vitro and plays a critical role in LIGHT (homologous to lymphotoxins, inducible expression, competes with herpesvirus glycoprotein D for herpesvirus entry mediator, a receptor expressed on T lymphocytes/LTβR interactions, leading to activation of non-canonical NF-κB signaling (74). In fact, knockdown of ZFP91 resulted in cessation of nuclear P52/RelB DNA binding, but has no effect on canonical p65 signaling.…”

Section: Working Like a Well-oiled Machine: Positive Regulation Of Nomentioning

confidence: 99%

Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology

McDaniel

Eden

Ringel

et al. 2016

Inflammatory Bowel Diseases

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Crohn’s disease and ulcerative colitis are common and debilitating manifestations of inflammatory bowel disease (IBD). IBD is characterized by a radical imbalance in the activation of pro-inflammatory and anti-inflammatory signaling pathways in the gut. These pathways are controlled by NF-κB, which is a master regulator of gene transcription. In IBD patients, NF-κB signaling is often dysregulated resulting in overzealous inflammation. NF-κB activation occurs through two distinct pathways, defined as either canonical or non-canonical. Canonical NF-κB pathway activation is well studied in IBD and is associated with the rapid, acute production of diverse pro-inflammatory mediators, such as COX-2, IL-1β, and IL-6. In contrast to the canonical pathway, the non-canonical or “alternative” NF-κB signaling cascade is tightly regulated and is responsible for the production of highly specific chemokines that tend to be associated with less acute, chronic inflammation. There is a relative paucity of literature regarding all aspects of non-canonical NF-κB signaling. However, it is clear that this alternative signaling pathway plays a considerable role in maintaining immune system homeostasis and likely contributes significantly to the chronic inflammation underlying IBD. Non-canonical NF-κB signaling may represent a promising new direction in the search for therapeutic targets and biomarkers associated with IBD. However, significant mechanistic insight is still required to translate the current basic science findings into effective therapeutic strategies.

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Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-κB pathway

Cited by 20 publications

References 22 publications

Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

ZFP91: A Noncanonical NF-κB Signaling Pathway Regulator with Oncogenic Properties Is Overexpressed in Prostate Cancer

Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology

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