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Suggest that Pygo2 has a tumor promoting function related to Wnt/ss-catenin signaling activity during intestinal tumor initiation and progression.
Transcriptional cofactors Bcl9 (show BCL9 Proteins), Bcl9l (show BCL9L Proteins) and Pygo1 (show PYGO1 Proteins)/2 act independently of beta-catenin (show CTNNB1 Proteins) to ensure proper enamel formation.
It analyzed Wnt1 (show WNT1 Proteins)-cre(+/-)::Pygo2(-/-) mice in which the beta-catenin (show CTNNB1 Proteins) co-activator gene, Pygopus 2 (Pygo2), is deleted specifically in neural crest cells.
These findings identify Pygo2 as an important regulator of Wnt (show WNT2 Proteins)/beta-catenin (show CTNNB1 Proteins) function in skin epithelia and p53 (show TP53 Proteins) activation as a prominent downstream event of beta-catenin (show CTNNB1 Proteins)/Pygo2 action in stem cell activation.
these results suggest that Pygo2 acts at a step downstream of mammary stem cell accumulation to facilitate transformation, and that it regulates the tumor initiating capacity and lineage preference of the already transformed mammary cells, in MMTV-Wnt1 (show WNT1 Proteins) mice.
even in the absence of the potentially redundant Pygo1 (show PYGO1 Proteins), Pygo2 does not require the H3K4me2/3 binding activity to sustain its function during mouse development
Mouse pygo2 expression was detected in the developing epidermis and hair follicles, which suggests that mpygo2 might mediate the effect of this signaling pathway in mouse skin.
In mammals, the Pygo1 (show PYGO1 Proteins)/Pygo2 genes are not absolutely required for canonical Wnt (show WNT2 Proteins) signaling in most developing systems, but rather function as quantitative transducers, or modulators, of Wnt (show WNT2 Proteins) signal intensity
Pygo2 can function in the Wnt (show WNT2 Proteins) pathway, but its activity in lens development is Wnt (show WNT2 Proteins) pathway-independent
ablation of pygo2 expression causes defects in morphogenesis of both ectodermally and endodermally derived tissues, including brain, eyes, hair follicles, and lung
Overexpression of Pygo2 facilitated the expression of P-glycoprotein, which acts as a drug efflux pump, by promoting the transcription of MDR1 at the MDR1 promoter loci, resulting in acceleration of the efflux of paclitaxel in human glioma cells.
We also determined the effect of Pygo2 on the sensitivity of breast tumors resistant to doxorubicin in a mouse model. Finally, RNA samples from 64 paired patient tumors (before and after chemotherapy) highly and significantly overexpressed Pygo2 and/or MDR1 after treatment, thus underlining a pivotal role for the Pygo2-mediated Wnt/b-catenin pathway in the clinical chemoresistance of breast cancer.
Findings are consistent with a model in which acetylation of Pygo2 by CBP/p300 (show CREBBP Proteins) family members in the active TCF (show HNF4A Proteins)/beta-catenin (show CTNNB1 Proteins) complex occurs coincident with histone acetylation and may be required for the recycling of Pygo2 away from the complex subsequent to target gene activation.
The activation of its expression by ERalpha (show ESR1 Proteins) and/or specificity protein-1 (SP1 (show SP1 Proteins)) suggests hPYGO2 as a theranostic target for hormone therapy responsive and refractory breast cancer.
Pygo2 functions as a prognostic factor for glioma due to its up-regulation of H3K4me3 and promotion of MLL1/MLL2 complex recruitment.
this study demonstrated that SNPs in the coding region of Pygo2 might be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility.
Our findings suggest that Pygopus-2 may be an important predictor of poor outcome in HCC (show FAM126A Proteins) patients, and could serve as a novel biomarker for HCC (show FAM126A Proteins).
Pygopus-2 over-expression is associated with hepatic carcinoma.
Pygo2 is a common node downstream of oncogenic Wnt (show WNT2 Proteins) and Akt (show AKT1 Proteins) signaling pathways.
We conclude that abnormal Pygo2 protein expression may be a marker for advanced non-small cell lung cancer
Involved in signal transduction through the Wnt pathway.
pygopus homolog 2
, pygopus 2