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Wnt signaling, named after the secreted proteins that bind to cell surface receptors to activate the pathway, plays critical roles both in embryonic development and the maintenance of homeostasis in many adult tissues. Two particularly important cellular programs orchestrated by Wnt signaling are proliferation and stem cell selfrenewal. Constitutive activation of the Wnt pathway resulting from mutation or improper modulation of pathway components contributes to cancer development in various tissues. Colon cancers frequently bear inactivating mutations of the adenomatous polyposis coli (APC) gene, whose product is an important component of the destruction complex that regulates β-catenin levels. Stabilization and nuclear localization of β-catenin result in the expression of a panel of Wnt target genes. We previously showed that Mule/ Huwe1/Arf-BP1 (Mule) controls murine intestinal stem and progenitor cell proliferation by modulating the Wnt pathway via c-Myc. Here we extend our investigation of Mule's influence on oncogenesis by showing that Mule interacts directly with β-catenin and targets it for degradation under conditions of hyperactive Wnt signaling. Our findings suggest that Mule uses various mechanisms to finetune the Wnt pathway and provides multiple safeguards against tumorigenesis.β-catenin | Mule | Wnt signaling | stem cells | colorectal cancer A ctivation of the Wnt pathway, named after the secreted proteins that bind to cell surface receptors to activate the pathway, plays a critical role in stem cell self-renewal, and thus the homeostasis of normal mammalian tissues. However, constitutive activation of Wnt signaling has been implicated in a broad range of cancers, including melanoma, hepatocellular carcinoma, and cancers of the prostate, thyroid, ovary, and breast (1-3). Perhaps the best-studied malignancy arising from the loss of regulation of the Wnt signaling pathway is colorectal cancer, which develops through a multistage process driven by the progressive accumulation of genetic mutations (4). The key initial activating mutation occurs in components of the Wnt pathway, but most commonly in APC.Canonical Wnt signaling involves a relay of protein interactions that serve to transmit a signal from the extracellular space to the plasma membrane. This signal is amplified in the cytoplasm and then directed to the nucleus to culminate in the activation of the Wnt target gene program. In molecular terms, when the glycoprotein Wnt is secreted into the extracellular space, it binds to a cell's Frizzled receptors in conjunction with the low-density lipoprotein receptorrelated proteins 5 and 6 (LRP5/6). The engagement of these receptors recruits the scaffolding protein Dishevelled (Dvl), leading to LRP5/6 phosphorylation and consequent recruitment of the scaffolding protein, Axin2 and glycogen synthase kinase 3 beta (GSK-3β). This recruitment results in disruption of the "destruction complex" that contains APC and normally binds to the signal transduction protein β-catenin to trigger its degradation. On Wn...

Background: USP7 is a ubiquitin-specific protease that regulates the turnover of target proteins in the cell. Results: UbE2E1 was identified to interact with USP7 through its ASTS motif. Conclusion: USP7 interacts with and deubiquitinates UbE2E1. Significance: USP7 regulates the stability of UbE2E1, the first example of a deubiquitinating enzyme, regulating an E2 conjugation enzyme.

A protocol was established for mass propagation of the valuable medicinal plant Ficus religiosa L. (Moraceae) through in vitro culture using apical and axillary buds of young sprouts from selected plants. Best shoot induction was observed on MS basal medium supplemented with 0.5 mg/l BAP + 0.1 mg/l IAA, in which 78 per cent of the explants produced 16 shoots per culture. Repeated subcultures in the same medium, resulted rapid shoot multiplication with 24 shoots per culture. In vitro raised shoots rooted on half strength MS supplemented with 2.0 mg/l IBA + 0.1 mg/l NAA. For acclimatization and transplantation, the plantlets in the rooting culture tubes were kept in normal room temperature for seven days before transplanting in pots where plantlets were reared for three weeks. The survival rate of regenerated plantlets was 85 per cent.

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