Gene Expression Atlas update--a value-added database of microarray and sequencing-based functional genomics experiments

Kapushesky, Misha; Adamusiak, Tomasz; Burdett, Tony; Culhane, Aedín C.; Farne, Anna; Filippov, A. V.; Holloway, Ele; Klebanov, Andrey; Kryvych, Nataliya; Kurbatova, Natalja; Kurnosov, Pavel; Malone, James; Melnichuk, Olga; Petryszak, Robert; Pultsin, Nikolay; Rustici, Gabriella; Tikhonov, Andrew; Travillian, Ravensara S.; Williams, Eleanor; Zorin, Andrey; Parkinson, Helen; Brāzma, Alvis

doi:10.1093/nar/gkr913

Cited by 144 publications

(125 citation statements)

References 19 publications

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“…The identity of the endogenous WNT ligand signaling through FZD7 remains unknown. Genome-wide expression profiling (RNA-seq) identified WNT3 as the most abundantly transcribed WNT gene in hESCs, consistent with publicly available expression data sets [e.g., the Gene Expression Atlas (19)]. In addition, several members of the RSPO gene family, which encode secreted molecules that augment WNT signaling activity (27)(28)(29), are expressed in hESCs.…”

Section: Discussionsupporting

confidence: 66%

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

Fernández

Huggins

Perna

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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WNT signaling is involved in maintaining stem cells in an undifferentiated state; however, it is often unclear which WNTs and WNT receptors are mediating these activities. Here we examined the role of the WNT receptor FZD7 in maintaining human embryonic stem cells (hESCs) in an undifferentiated and pluripotent state. FZD7 expression is significantly elevated in undifferentiated cells relative to differentiated cell populations, and interfering with its expression or function, either by short hairpin RNA-mediated knockdown or with a fragment antigen binding (Fab) molecule directed against FZD7, disrupts the pluripotent state of hESCs. The FZD7-specific Fab blocks signaling by Wnt3a protein by downregulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/β-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/β-catenin signaling through FZD7 to maintain an undifferentiated phenotype. human pluripotent stem cell | self-renewal | differentiation

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Section: Discussionsupporting

confidence: 66%

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

Fernández

Huggins

Perna

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…3a and S1), functional insights can be gained by determining which domain(s) is (are) responsible for a phenotype. As VASP domain organization is conserved, its expression is relatively high in the colon (Kapushesky et al, 2012) and reagents for the analysis of VASP were readily available, we selected VASP for use in all subsequent analyses.…”

Section: Resultsmentioning

confidence: 99%

Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

2015

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Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells.

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“…According to the EMBL-EBI Expression Atlas, DCoH2 (PCBD2) is typically expressed at 5-20-fold lower levels than DCoH1 (PCBD1) in many organs (compare ENSG00000132570 and ENSG00000166228) (45). The DCoH2 homotetramer may therefore be available to assure low levels of DCoH activity, for example interacting with HNF-1 as shown in DCoH1 null mutant mice (25).…”

Section: Discussionmentioning

confidence: 99%

Interactions with the Bifunctional Interface of the Transcriptional Coactivator DCoH1 Are Kinetically Regulated

Wang

Coco

Rose

2015

Journal of Biological Chemistry

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Background:The protein dimerization cofactor of HNF-1 (DCoH1)/pterin-carbinolamine dehydratase (PCD) accomplishes two unrelated activities, forming two complexes with the same interface. Results: The DCoH1 homotetramer is kinetically trapped; a single mutation in the interface increases the unfolding rate 10 9 -fold. Conclusion: Kinetic regulation allows DCoH to assume two unrelated functions. Significance: Mutations excluding water from interfaces represent kinetic "hot spots," dramatically affecting dissociation rates.

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Gene Expression Atlas update--a value-added database of microarray and sequencing-based functional genomics experiments

Cited by 144 publications

References 19 publications

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

Interactions with the Bifunctional Interface of the Transcriptional Coactivator DCoH1 Are Kinetically Regulated

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