Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation

Zhao, Jun; Liu, Shuizhong; Wang, Hongwei; Zhang, Xiaomei; Kang, Tiejiang; Li, Zhanyi; Deng, Hemin; Wu, Yue; Cao, Shujie

doi:10.1016/j.jocn.2010.11.009

Cited by 20 publications

(34 citation statements)

References 30 publications

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“…Therefore, MAD2B plays a crucial role in proper mitotic progression and faithful DNA replication. Accumulating evidence indicated that MAD2B is overexpressed in tumor genesis and tightly correlated with the progression and prognosis of these malignancies, such as colon cancer, epithelial ovarian cancer, and glioma (2,19,20,31). Previously, we reported that hyperglycemia mediates neuronal apoptosis through inducing the production of MAD2B, which represents a novel mechanism of diabetic encephalopathy (17).…”

mentioning

confidence: 95%

MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis

Tang

Fan

et al. 2016

American Journal of Physiology-Renal Physiology

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MAD2B, an anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase ζ, is indispensible for mitotic checkpoint control and DNA repair. Previously, we established that MAD2B is expressed in glomerular and tubulointerstitial compartments and participates in high glucose-induced podocyte injury. However, its role in other renal diseases remains elusive. In the present study, we aim to illustrate the potential role of MAD2B in the pathogenesis of renal fibrosis. By immunofluorescence and Western blotting, we found MAD2B expression is obviously increased in tubulointerstitial fibrosis (TIF) patients and unilateral ureteral obstruction (UUO) mice. It is widely accepted that resident fibroblasts are the major source of collagen-producing myofibroblasts during TIF. Therefore, we evaluated the level of MAD2B in fibroblasts (NRK-49F) exposed to transforming growth factor (TGF)-β1 by immunoblotting and revealed that MAD2B is upregulated in a time-dependent manner. Intriguingly, SnoN, a transcriptional repressor of the TGF-β1/Smad signaling pathway, is decreased in TGF-β1-treated fibroblasts as well as the kidney cortex from TIF patients and UUO mice. Either in vitro or in vivo, local genetic depletion of MAD2B by lentiviral transfection could preserve SnoN abundance and suppress Smad3 phosphorylation, which finally dampens fibroblast activation, ECM accumulation, and alleviates the severity of TIF. However, the ubiquitin ligase APC/C is not involved in the MAD2B-mediated SnoN decline, although this process is ubiquitination dependent. In conclusion, our observation proposes that besides cell cycle management, MAD2B has a profibrotic role during fibroblast activation and TIF by suppressing SnoN expression. Targeting the MAD2B-SnoN pathway is a promising intervention for TIF.

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mentioning

confidence: 95%

MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis

Tang

Fan

et al. 2016

American Journal of Physiology-Renal Physiology

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“…In addition, MAD2B interacts with TCF4 and regulates the Wnt/β-catenin signaling pathway [20]. Most studies on MAD2B have focused on its role in cancer and neurological diseases [13,14,15,21,22,23], but it is still unknown about its expression and function in the kidney.…”

Section: Discussionmentioning

confidence: 99%

“…MAD2B regulates cell cycle progression by binding to CDH1 or CDC20 and inhibiting the activity of APC/C [11,12]. MAD2B levels are upregulated in many malignant tumors, and correlate with tumor stage and poor prognosis, probably due to mitotic failure and genetic instability caused by the inhibition of APC/C [13,14,15]. We previously used immunohistochemistry to demonstrate that MAD2B protein levels were increased in the kidney glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice, the db/db model of type 2 diabetes, and kidney biopsies of patients with diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Glomerular Endothelial Cells from High Glucose-Induced Injury by Blockade of MAD2B

Wang

Yu²,

Meng

et al. 2015

Cell Physiol Biochem

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Background/Aims: To assess the role of mitotic arrest-deficient 2-like protein 2 (MAD2B) in high glucose-induced injury in mouse glomerular endothelial cells (GEnCs). Methods: GEnCs were cultured in vitro, and MAD2B protein levels were measured by Western blot in cells stimulated with high glucose (30 mM) for various periods of time. MAD2B and scrambled shRNA were introduced into GEnCs by liposomal transfection. Cell proliferation, apoptosis, nitric oxide (NO) production, and monolayer permeability were then measured in cells grown in the following conditions: control, high glucose treatment, MAD2B shRNA transfection with high glucose treatment, and scrambled shRNA transfection with high glucose treatment. Results:High glucose increased the protein levels of MAD2B in GEnCs. Compared with control cells, apoptosis was increased by high glucose treatment, which was attenuated by transfection with MAD2B shRNA transfection. Cells treated with high glucose produced less NO than control cells, whereas MAD2B shRNA transfection increased NO production. Cell monolayer permeability was enhanced in high glucose treated cells, but MAD2B shRNA transfection reduced permeability. Conclusion: High glucose levels induced the expression of MAD2B in GEnCs, whereas suppressing its expression reduced high glucose-induced endothelial cell apoptosis and high permeability, and promoted cell proliferation and NO production.

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“…Mitotic arrest deficient 2 (Mad2), an essential spindle checkpoint protein, is another important protein involved in the induction of CIN in glioma [129]. Mad2 is overexpressed in several tumor types, including glioblastoma.…”

Section: Inflammation Oxidative Stress and Genetic Instability Inmentioning

confidence: 99%

The Process and Regulatory Components of Inflammation in Brain Oncogenesis

et al. 2017

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Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α(TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers. The roles of reactive astrocytes, tumor associated microglia and macrophages, metabolic alterations, microsatellite instability, O6-methylguanine DNA methyltransferase (MGMT) DNA repair and epigenetic alterations mediated by the isocitrate dehydrogenase 1 (IDH1) mutations have been discussed. The inflammatory pathways with relevance to the brain cancer treatments have been highlighted.

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Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation

Cited by 20 publications

References 30 publications

MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis

MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis

Attenuation of Glomerular Endothelial Cells from High Glucose-Induced Injury by Blockade of MAD2B

The Process and Regulatory Components of Inflammation in Brain Oncogenesis

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