RGD Reference Report - Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer.

Authors: Chen, Chenbin  Sun, Xiangwei  Xie, Wangkai  Chen, Sian  Hu, Yuanbo  Xing, Dong  Xu, Jianfeng  Chen, Xiaodong  Zhao, Zhiguang  Han, Zheng  Xue, Xiangyang  Shen, Xian  Lin, Kezhi 
Citation: Chen C, etal., Cell Death Dis. 2020 Jul 8;11(7):514. doi: 10.1038/s41419-020-2718-3.
RGD ID: 152025196
Pubmed: PMID:32641734   (View Abstract at PubMed)
PMCID: PMC7343808   (View Article at PubMed Central)
DOI: DOI:10.1038/s41419-020-2718-3   (Journal Full-text)

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomach cancer severityIEP 152025196protein:altered expression:nucleus and cytoplasm (human)RGD 
stomach cancer severityISODAXX (Homo sapiens)152025196; 152025196protein:altered expression:nucleus and cytoplasm (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Daxx  (death-domain associated protein)

Genes (Mus musculus)
Daxx  (Fas death domain-associated protein)

Genes (Homo sapiens)
DAXX  (death domain associated protein)


Additional Information