A transphyletic approach to analyzing evolutionarily conserved β-catenin modules
Ontology highlight
ABSTRACT:
ORGANISM(S): Cellular Organisms Xenopus Laevis
SUBMITTER: Hiroshi Watanabe
PROVIDER: PXD035167 | JPOST Repository | Sat Jul 08 00:00:00 BST 2023
REPOSITORIES: jPOST
Dataset's files
Similar Datasets
Project description:β-catenin plays a vital role in various biological processes, such as body axis determination and cell differentiation, during embryonic development in metazoans. These β-catenin functions are thought to be exerted through complexes formed with various types of proteins. Although β-catenin complex proteins have been identified in several bilaterian models, little is known about the structural and functional properties of β-catenin complexes in the early metazoan evolutionary phases. In this study, we performed a comparative analysis of β-catenin sequences in nonbilaterian lineages that branched off early in metazoan evolution. We aslo carried out a transphyletic function experiments of β-catenin from non-bilaterian metazoans using developing Xenopus embryos, which included secondary axis induction in embryos and proteomic analysis of the β-catenin protein complex. Comparative functional analysis of nonbilaterian β-catenins also demonstrated sequence characteristics important for β-catenin function, and the deep origin and evolutionary conservation of the cadherin-catenin complex. Proteins coimmunoprecipitated with β-catenin included several proteins conserved across metazoans. These data provide a new insight into the conserved repertoire of β-catenin complexes.
2025-01-21 | PXD053223 | JPOST Repository
Project description:The aim of our study is to identify direct target genes of Wnt/β-catenin signaling operating in gastrula-stage X. tropicalis embryos. We characterized the genomic loci bound by the Wnt signaling downstream component β-catenin in intact X. tropicalis gastrulae using ChIP-seq. We also determined the normal mRNA expression profile in control (uninjected and control-MO-injected) embryos and altered mRNA expression profiles in two experimental samples: embryos where endogenous wnt8a function was knocked down with wnt8a MO, and where we experimentally re-instated Wnt8a expression with a DNA construct (pCSKA-wnt8a) in the same wnt8a knock down.
2016-04-25 | GSE72657 | GEO
Project description:During Xenopus gastrulation, dorsal stabilization of β-Catenin at the earliest stage and subsequent target genes expression are critical for dorsal-ventral axis determination. However, many β-Catenin targets that mediate this process are still unkown. Here through RNA-seq analysis of β-Catenin knockdown embryos and self-regulating dorsal and ventral half embryos at early gastrula, we define an early β-Catenin gene signature that is downregulated by β-Catenin MO and enriched in dorsal gastrula tissues. This gene signature includes classic Spemann organizer genes, as well as other novel genes. Further analyses revealed that the early β-Catenin gene signature is positively correlated with LiCl treated, Wnt8 and Siamois mRNA-induced genes, consistent with their early role in dorsal-ventral axis formation. Our results also show that St 10.5 is the appropriate stage to uncover β-Catenin target genes that regulate dorsal-ventral patterning than St 9. Meanwhile, the multi-growth factor antagonist Cerberus inhibits part of the early β-Catenin gene signature and also controls the expression of a unique set of genes. Our findings provide new insight into the pivotal role of β-catenin in dorsal-ventral axis determination and can serve a fruitful resource for this field.
2017-03-15 | GSE93195 | GEO
Project description:Breast carcinoma amplified sequence 2 (BCAS2), a core component of the hPrP19 complex, plays crucial roles in various physiological and pathological processes. However, whether BCAS2 has functions other than being a key RNA-splicing regulator within the nucleus remains unknown. Here, we show that BCAS2 is essential for primitive hematopoiesis in zebrafish and mouse embryos. The activation of Wnt/β-catenin signal, which is required for hematopoietic progenitor differentiation, is significantly decreased upon depletion of bcas2 in zebrafish embryos and mouse embryonic fibroblasts (MEFs). Interestingly, BCAS2 deficiency has no obvious impact on the splicing efficiency of β-catenin pre-mRNA, while significantly attenuating β-catenin nuclear accumulation. Moreover, we find that BCAS2 directly binds to β-catenin via its coiled-coil domains, thereby sequestering β-catenin within the nucleus. Thus, our results uncover a previously unknown function of BCAS2 in promoting Wnt signaling by enhancing β-catenin nuclear retention during primitive hematopoiesis.
2025-06-05 | GSE297155 | GEO
Project description:Protein synthesis is a universal process mainly regulated at the initiation stage to permit a rapid and reversible control of cellular and environmental changes. Several stress conditions such as hypoxia, activate the translational reprogramming of mRNAs encoding proteins essential for stress recovery and cell survival. Increasing evidence of unconventional translation initiation mechanisms lead by 5’UTR motifs, shows the cells potential to adapt their translation machinery in response to different stimuli. β-catenin is an oncogenic protein playing an essential role in Wnt signal transduction. Dysregulation of this pathway causes aberrant nuclear β-catenin accumulation, which consequently modulates the expression of genes related to cancer development and metastasis. To date, the mechanism of its translation maintenance in stressed cells remains elusive. To understand how β-catenin mRNA escapes global translational blockade in hypoxic cancer cells, we determined the 5’UTR secondary structure and searched for translation regulatory elements in living cells. We found that a three-way junction (TWJ) within its 5’UTR is involved in the translation efficiency (TE) of β-catenin and its enhancement under hypoxia. We showed that the TWJ single-stranded polypurine region becomes, in the absence of eIF4E, an alternative anchoring site for eIF4B, eIF4A and eIF4G. Importantly, the TWJ makes the β-catenin mRNA translation eIF4A-dependent being sensible to silvestrol, a selective eIF4A inhibitor and promising anticancer agent. Our study unravels the 5’UTR-driven translation regulation mechanism of β-catenin mRNA and set the basis to explore its inhibition in the frame of cancer progression.
2025-05-06 | PXD045451 | Pride
Project description:Embryonic genome activation (EGA) is orchestrated by an intrinsic developmental program initiated during oocyte maturation with translation of stored maternal mRNAs. Here we show that tankyrase, a poly(ADP-ribosyl) polymerase that regulates β-catenin levels, undergoes programmed translation during oocyte maturation and serves an essential role in mouse EGA. Newly translated TNKS triggers proteasomal degradation of axin, reducing targeted destruction of β-catenin and promoting β-catenin-mediated transcription of target genes, including Myc. MYC mediates ribosomal RNA transcription in 2-cell embryos, supporting global protein synthesis. Suppression of tankyrase activity using knockdown or chemical inhibition causes loss of nuclear β-catenin and global reductions in transcription and histone H3 acetylation. Chromatin and transcriptional profiling indicate that development arrests prior to the mid-2-cell stage, mediated in part by reductions in β-catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational β-catenin activation and is required to complete EGA.
2020-05-21 | GSE123815 | GEO
Project description:β-Catenin is a regulator of cutaneous wound repair. The expression of genes that are modulated in response to changes in β-Catenin levels (stabilization and downregulation) in cutaneous mouse wounds, post injury, during the proliferative phase of repair, was investigated. We are particularly interested in genes that are modulated (in opposite directions) in response to both the induction (stabilization) versus downregulation of β-Catenin. To investigate this, conditional β-Catenin stabilized (Harada, N., et al. EMBO J. 1999 Nov 1;18(21):5931-42) mice were injected with either a Cre-expressing adenovirus, or a GFP-expressing control virus, three days following injury, and wounds were harvested eight days post injury. For conditional knockdown of β-Catenin, mice generated from a cross between conditional β-Catenin knockdown mice (Brault, V. et al., Development. 2001 Apr;128(8):1253-64), and mice that express a tamoxifen-inducible form of Cre (Hayashi, S., and McMahon, A.P., Dev Biol. 2002 Apr 15;244(2):305-18), were treated with Tamoxifen for five days, beginning at the third day after injury. Wounds were harvested eight days after wounding. This provides insight into the identities of genes modulated in response to changes in β-Catenin levels during the proliferative stage of cutaneous wound repair.
2018-12-31 | GSE50153 | GEO
Project description:β-Catenin is a regulator of cutaneous wound repair. The expression of genes that are modulated in response to changes in β-Catenin levels initiated prior to injury was investigated during the proliferative phase of repair. We are particularly interested in genes that are modulated (in opposite directions) in response to both the induction ('stabilization') versus downregulation of β-Catenin. To investigate this, conditional β-Catenin stabilized mice (Harada, N., et al. EMBO J. 1999 Nov 1;18(21):5931-42) were injected with either a Cre-expressing adenovirus, or a GFP-expressing control virus, four days prior to injury, and wounds were harvested eight days following injury. For conditional knockdown of β-Catenin, mice generated from a cross between conditional β-Catenin knockdown mice (Brault, V. et al., Development. 2001 Apr;128(8):1253-64), and mice that express a tamoxifen-inducible form of Cre (Hayashi, S., and McMahon, A.P., Dev Biol. 2002 Apr 15;244(2):305-18), were treated with Tamoxifen for five days prior to injury. Wounds were harvested eight days after wounding. This provides insight into gene expression changes that occur during the proliferative stage of cutaneous wound repair in response to changes in β-Catenin levels initiated before/at the time of injury.
2018-12-31 | GSE50152 | GEO
Project description:The five-year survival rate for non-small-cell lung cancer (NSCLC) remains poor, primarily due to tumor invasion and metastasis. This study evaluates the anti-metastatic potential of the oncolytic virus OH2 in NSCLC. OH2 inhibits migration and invasion of NSCLC by downregulating β-catenin, as demonstrated in vitro and an in a lung metastasis model. OH2 reduces β-catenin mRNA levels, suppressing its transcriptional activity and downstream expression of Matrix Metalloproteinases (MMPs), key mediators of extracellular matrix degradation. Proteomic analysis of the secretome confirms reduced MMPs expression following OH2 treatment. Mechanistically, the OH2 tegument protein UL41 is identified as a critical factor that degrades β-catenin mRNA, thus inhibiting β-catenin nuclear transcriptional activity. These findings reveal a novel anti-metastatic mechanism of OH2 via disruption of the β-catenin/MMPs axis and support its potential as a therapeutic candidate for invasive NSCLC.
2025-07-27 | PXD065329 | Pride
Project description:Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer. Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways. Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05). Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer. For the microarray experiment, we selected fresh frozen primary cervical cancer tissue, containing at least 80% tumor cells, of patients with histologically confirmed N0 (n=20) and of patients with N+ (n=19). The N0 and N+ groups were matched for age, FIGO stage and histology (all squamous cell carcinoma).
2011-02-15 | E-GEOD-26511 | biostudies-arrayexpress