Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity

Duke‐Cohan, Jonathan S.; Ishikawa, Yuki; Yoshizawa, Akihiro; Choi, Young-Il; Lee, Chin-Nien; Acuto, Oreste; Kissler, Stephan; Reinherz, Ellis L.

doi:10.1126/scisignal.aan8799

Cited by 17 publications

(25 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Single-nucleotide polymorphisms in TAGAP are associated with a variety of autoimmune diseases. Some researchers have put forward that TAGAP variation modulates the risk of autoimmunity by altering thymocyte migration during thymic selection [18]. Mutations in the ABCC8 gene are closely related to diabetes [19,20].…”

Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Wang

Zhu

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Objective. A survival risk assessment model associated with a lung adenocarcinoma (LUAD) microenvironment was established and evaluated to identify effective independent prognostic factors for LUAD. Methods. The public data were downloaded from the TCGA database, and ESTIMATE prediction software was used to score immune cells and stromal cells for tumor purity prediction. The samples were divided into the high-score group and the low-score group by the median value of the immune score (or stromal score). The Wilcoxon test was used for differential analysis. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) was performed using “clusterProfiler” of R package. Meanwhile, univariate and multivariate regression analysis was performed on DEGs to construct a multivariate Cox risk regression model with variable gene expression levels as independent prognostic factors affecting a tumor microenvironment (TME) and tumor immunity. Results. This study found that LUAD patients with high immune cell (stromal cell) infiltration had better prognosis and were in earlier staging. Functional enrichment analysis revealed that most DEGs were related to the proliferation and activation of immune cells or stromal cells. A survival prediction model composed of 6 TME-related genes (CLEC17A, TAGAP, ABCC8, BCAN, FLT3, and CCR2) was established, and finally, the 6 feature genes closely related to the prognosis of LUAD were proved. The AUC value of the ROC curve in this model was 0.7, indicating that the model was reliable. Conclusion. Six genes related to the LUAD microenvironment have a predictive prognostic value in LUAD.

show abstract

Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Wang

Zhu

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…As for ACTC1, TAGAP overexpression improved recombinant protein secretion. TAGAP enzymatic activity was showed to regulate the organization of actomyosin fibril, to release integrin‐mediated adhesion in thymocytes, which is necessary for directed‐thymocyte migration from the cortex to the medulla (Duke‐Cohan et al, 2018). In suspension CHO cells, TAGAP could function as a mediator for intracellular cytoskeleton signal to cell surface integrins, hence improving cell proliferation, viability, and adaptation to suspension.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Consistently, ACTC1 deficiency has been mainly linked to heart diseases (Debold et al, 2010; Wang et al, 2016). TAGAP is a signaling protein that was involved in thymocyte loss of adhesion and thymocyte and T cells cytoskeleton reorganization (Connelly et al, 2014; Duke‐Cohan et al, 2018). Alterations of the TAGAP gene have been associated with various autoimmune diseases (Eyre et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of cytoskeleton organization on recombinant protein expression by CHO cells

Pourcel

Buron

Arib³

et al. 2020

Biotech & Bioengineering

View full text Add to dashboard Cite

In this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. Two cytoskeletal genes, Actin alpha cardiac muscle 1 (ACTC1) and a guanosine triphosphate GTPase‐activating protein (TAGAP), were found to be upregulated in highly productive therapeutic protein‐expressing Chinese hamster ovary (CHO) cells selected by the deprivation of vitamin B5. We report here that the overexpression of the ACTC1 protein was able to improve significantly recombinant therapeutic production, as well as to decrease the levels of toxic lactate metabolic by‐products. ACTC1 overexpression was accompanied by altered as well as decreased polymerized actin, which was associated with high protein production by CHO cell cultured in suspension. We suggest that the depolymerization of actin and the possible modulation of integrin signaling, as well as changes in basal metabolism, may be driving the increase of protein secretion by CHO cells.

show abstract

“…Tagap is a signaling protein member of the Rho GTPase‐activating protein (GAP) family. In thymocytes, it was shown to regulate the abundance of active RhoA, thus promoting cytoskeleton reorganization and release of β1‐integrin‐mediated adhesion allowing thymocytes migration from the cortex to the medulla (Duke‐Cohan et al, 2018). Moreover, Tagap and the cardiac muscle actin alpha (ACTC1) were found to be upregulated in vitamin B5‐selected cells producing therapeutic proteins at very high levels, and Tagap overexpression was shown to increase the expression of ACTC1, which in turn increases the production of various therapeutic proteins (see accompanying paper, Pourcel, Buron, Arib, et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of transcription factor Foxa1 and target genes remediate therapeutic protein production bottlenecks in Chinese hamster ovary cells

Berger

Fourn²,

Masternak

et al. 2020

Biotech & Bioengineering

View full text Add to dashboard Cite

Despite extensive research conducted to increase protein production from Chinese hamster ovary (CHO) cells, cellular bottlenecks often remain, hindering high yields. In this study, a transcriptomic analysis led to the identification of 32 genes that are consistently upregulated in high producer clones and thus might mediate high productivity. Candidate genes were associated with functions such as signaling, protein folding, cytoskeleton organization, and cell survival. We focused on two engineering targets, Erp27, which binds unfolded proteins and the Erp57 disulfide isomerase in the endoplasmic reticulum, and Foxa1, a pioneering transcription factor involved in organ development. Erp27 moderate overexpression increased production of an easy‐to‐express antibody, whereas Erp27 and Erp57 co‐overexpression increased cell density, viability, and the yield of difficult‐to‐express proteins. Foxa1 overexpression increased cell density, cell viability, and easy‐ and difficult‐to‐express protein yields, whereas it decreased reactive oxygen species late in fed‐batch cultures. Foxa1 overexpression upregulated two other candidate genes that increased the production of difficult‐ and/or easy‐to‐express proteins, namely Ca3, involved in protecting cells from oxidative stress, and Tagap, involved in signaling and cytoskeleton remodeling. Overall, several genes allowing to overcome CHO cell bottlenecks were identified, including Foxa1, which mediated multiple favorable metabolic changes that improve therapeutic protein yields.

show abstract

Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity

Cited by 17 publications

References 57 publications

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Influence of cytoskeleton organization on recombinant protein expression by CHO cells

Overexpression of transcription factor Foxa1 and target genes remediate therapeutic protein production bottlenecks in Chinese hamster ovary cells

Contact Info

Product

Resources

About