CDK2 and PKA Mediated-Sequential Phosphorylation Is Critical for p19INK4d Function in the DNA Damage Response

DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with 32P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage

Effects of Elemental Sulfur on Soil pH and Growth of Saskatoon Berry (<i>Amelanchier alnifolia</i>) and Beaked Hazelnut (<i>Corylus cornuta</i>) Seedlings

The land disturbed by open-pit oil sands mining must be restored to support the survival and growth of native boreal plants. Because tailings sand and sodic shale overburden are commonly used as an underlying parent substrate that is capped by boreal forest cover soils, the soil pH in reclamation sites is often higher compared with undisturbed boreal forest soil. Sulfur is a major byproduct of oil sands refining and could potentially be used as an amendment to lower the soil pH on reclamation sites. In this study, we examined the effects of soil pH and elemental sulfur on growth and physiological responses in Saskatoon berry and beaked hazelnut seedlings. We found that elemental sulfur was effective in lowering soil pH. However, addition of elemental sulfur to a forest soil of pH 5.7 lowered the soil pH to around 3, which impaired the growth and physiological performance of both plant species. The addition of 5 and 25 g kg−1 elemental sulfur to the pH 8.5 soil did not substantially improve the examined growth and physiological parameters in Saskatoon berry and beaked hazelnut seedlings. Further, excess addition of elemental sulfur in high pH soil could reduce the uptake of nitrogen, phosphorus, and calcium in Saskatoon berry. The results demonstrate that the amount of sulfur applied to the soil would need to be carefully determined for different soil types and pH levels to avoid potential toxicity effects

Effects of Elemental Sulfur on Soil pH and Growth of Saskatoon Berry (Amelanchier alnifolia) and Beaked Hazelnut (Corylus cornuta) Seedlings

The land disturbed by open-pit oil sands mining must be restored to support the survival and growth of native boreal plants. Because tailings sand and sodic shale overburden are commonly used as an underlying parent substrate that is capped by boreal forest cover soils, the soil pH in reclamation sites is often higher compared with undisturbed boreal forest soil. Sulfur is a major byproduct of oil sands refining and could potentially be used as an amendment to lower the soil pH on reclamation sites. In this study, we examined the effects of soil pH and elemental sulfur on growth and physiological responses in Saskatoon berry and beaked hazelnut seedlings. We found that elemental sulfur was effective in lowering soil pH. However, addition of elemental sulfur to a forest soil of pH 5.7 lowered the soil pH to around 3, which impaired the growth and physiological performance of both plant species. The addition of 5 and 25 g kg&minus;1 elemental sulfur to the pH 8.5 soil did not substantially improve the examined growth and physiological parameters in Saskatoon berry and beaked hazelnut seedlings. Further, excess addition of elemental sulfur in high pH soil could reduce the uptake of nitrogen, phosphorus, and calcium in Saskatoon berry. The results demonstrate that the amount of sulfur applied to the soil would need to be carefully determined for different soil types and pH levels to avoid potential toxicity effects

Evidence for a p27 tumor suppressive function independent of its role regulating cell proliferation in the prostate

Reduced p27 levels correlate with poor prognosis in a wide spectrum of human tumors and can accelerate tumorigenesis in mouse tissues. To determine whether p27 deficiency can accelerate tumorigenesis in tissues with inactive Rb and p53 pathways, we examined the effect of p27 status on prostate tumorigenesis in mice expressing simian virus 40 large T antigen (LT). In p27-deficient mice expressing LT, tumors progressed from high-grade prostatic intraepithelial neoplasia to poorly differentiated carcinoma at a greatly accelerated rate. p27 deficiency could not collaborate with a mutant of LT that fails to inactivate the Rb pathway alone. Furthermore, p27 deficiency does not increase the proliferation index, reduce the apoptotic index, or affect the expression of E2F-dependent genes in cells expressing LT at any stage of the disease. Expression of LT alone leads to maximal proliferation, but p27 deficiency still increases the amount of cyclin A and cyclin-dependent kinase 2-associated kinase activity in tissues. Interestingly, this model recapitulates an important feature of the human disease, specifically a high frequency of allelic loss of chromosome 16q, which is syntenic to mouse chromosome 8. Loss of heterozygosity may accelerate the inactivation of other tumor suppressors, such as E-cadherin, which are located in this interval. These experiments provide direct physiological and causal evidence that p27 has tumor suppressive functions independent of its role regulating cell proliferation

I ONLY HAVE EYES FOR YOU / Warren (Harry). AT THE PROM / Carey et Johnson. LOVE WALKED IN / Gershwin (G.) et Gershwin (I.). YOURS / Roig et Scherr ; Les Flamingos

Titre uniforme : [I only have eyes For you]Titre uniforme : [Love walked in]BnF-Partenariats, Collection sonore - BelieveContient une table des matière