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Biomedical Science

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on Tue, 01/30/2018 - 04:11

Biology, Medicine, Health and Nutrition Science

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Ubiquitination governs oscillation of cyclin-dependent kinase (CDK) activity through a periodic degradation of cyclins for orderly cell cycle progression; however, the mechanism that maintains the constant CDK protein levels throughout the cell cycle remains unclear. Here we show that CDK6 is modified by small ubiquitin-like modifier-1 (SUMO1) in glioblastoma, and that CDK6 SUMOylation stabilizes the protein and drives the cell cycle for the cancer development and progression. CDK6 is also a substrate of ubiquitin; however, CDK6 SUMOylation at Lys 216 blocks its ubiquitination at Lys 147 and inhibits the ubiquitin-mediated CDK6 degradation. Throughout the cell cycle, CDK1 phosphorylates the SUMO-specific enzyme, ubiquitin-conjugating enzyme9 (UBC9) that in turn mediates CDK6 SUMOylation during mitosis; CDK6 remains SUMOylated in G1 phase and drives the cell cycle through G1/S transition. Thus, SUMO1-CDK6 conjugation constitutes a mechanism of cell cycle control and inhibition of this SUMOylation pathway may provide a strategy for treatment of glioblastoma.

PMID:
24953629
PMCID:
PMC4090607
DOI:
10.1038/ncomms5234
[Indexed for MEDLINE] 

https://www.ncbi.nlm.nih.gov/pubmed/24953629

 

 

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Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139373/

 

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ZNF544 Gene(Protein Coding)

Zinc Finger Protein 544

https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF544

 

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Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.

https://www.ncbi.nlm.nih.gov/pubmed/18821565

 

 

 

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AC010642.1 (Clone-based (Ensembl) gene)

RefSeq

No overlapping RefSeq annotation found

Ensembl version

ENSG00000269794.1

http://useast.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000269794;r=...

 

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NQO2 Gene(Protein Coding)

N-Ribosyldihydronicotinamide:Quinone Reductase 2

https://www.genecards.org/cgi-bin/carddisp.pl?gene=NQO2

 

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ROVE2 Gene(Protein Coding) 
TROVE Domain Family Member 2
 
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CNOT1 Gene(Protein Coding) 
CCR4-NOT Transcription Complex Subunit 1
 
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Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis.

 

https://www.ncbi.nlm.nih.gov/pubmed/28525947

 

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Early-Phase Study to Assess Inhibitor Ribociclib in Patients With Recurrent Glioblastoma or Anaplastic Glioma

https://clinicaltrials.gov/ct2/show/NCT02345824?term=cdk6&cond=Glioblast...

 

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SYNE1 spectrin repeat containing nuclear envelope protein 1 [ Homo sapiens (human) 

https://www.ncbi.nlm.nih.gov/gene?term=NM_033071

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Defining the environmental context in which genes enhance disease susceptibility can provide insight into the pathogenesis of complex disorders. We report that the intra-uterine environment modulates the association of schizophrenia with genomic risk (in this study, genome-wide association study–derived polygenic risk scores (PRSs)). In independent samples from the United States, Italy, and Germany, the liability of schizophrenia explained by PRS is more than five times greater in the presence of early-life complications (ELCs) compared with their absence. Patients with ELC histories have significantly higher PRS than patients without ELC histories, which is confirmed in additional samples from Germany and Japan. The gene set composed of schizophrenia loci that interact with ELCs is highly expressed in placenta, is differentially expressed in placentae from complicated in comparison with normal pregnancies, and is differentially upregulated in placentae from male compared with female offspring. Pathway analyses reveal that genes driving the PRS-ELC interaction are involved in cellular stress response; genes that do not drive such interaction implicate orthogonal biological processes (for example, synaptic function). We conclude that a subset of the most significant genetic variants associated with schizophrenia converge on a developmental trajectory sensitive to events that affect the placental response to stress, which may offer insights into sex biases and primary prevention

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DS Vinay, EP Ryan, G PawelecWH Talib… - Seminars in cancer …, 2015 - Elsevier

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through “equilibrium” and …

 

https://www.sciencedirect.com/science/article/pii/S1044579X1500019X

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Applications of DNA-based liquid biopsy for central nervous system neoplasms
J Wang, C Bettegowda - The Journal of Molecular Diagnostics, 2017 - Elsevier
The management of central nervous system malignancies remains reliant on histopathological analysis and neuroimaging, despite their complex genetic profile. The intratumoral heterogeneity displayed by these tumors necessitates a more sophisticated method of tumor analysis and monitoring, with the ability to assess tumors over space and time. Circulating biomarkers, including circulating tumor cells, circulating tumor DNA, and extracellular vesicles, hold promise as a type of real-time liquid biopsy able to provide …
  Cited by 10 Related articles All 6 versions
 
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[HTML] Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis

X Jiang, Y Huang, X Wang, Q Liang, Y Li, F Li… - Biomedicine & …, 2017 - Elsevier
The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in …
 
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Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM  WR Wiedemeyer, IF Dunn, SN Quayle… - Proceedings of the …, 2010 - National Acad Sciences Glioblastoma multiforme (GBM) is a fatal primary brain tumor harboring myriad genetic and epigenetic alterations. The recent multidimensional analysis of the GBM genome has provided a more complete view of the landscape of such alterations and their linked pathways. This effort has demonstrated that certain pathways are universally altered, but that the specific genetic events altered within each pathway can vary for each particular patient9s tumor. With this atlas of genetic and epigenetic events, it now becomes feasible to …  

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MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting …

W Chen, XK Xu, JL Li, KK Kong, H Li, C Chen, J He… - Oncotarget, 2017 - ncbi.nlm.nih.gov
Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited therapeutic options. Temozolomide (TMZ) is a novel cytotoxic agent used as first-line chemotherapy for GBM, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. By using the HiSeq sequencing and bioinformatics methods, we identified lncRNAs showing different expression levels in TMZ-resistant and non-resistant patients. RT-qPCR was then performed in tissues and serum …

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