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β-Catenin-Dependent and -Independent Effects of ΔN-Plakoglobin on Epidermal Growth and Differentiation

机译:β-Catenin依赖性和非依赖性的ΔN-珠蛋白对表皮生长和分化的影响

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Both β-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. β-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (ΔN122-PG) lacking the glycogen synthase kinase 3β phosphorylation sites and therefore protected against degradation (transgenic line K5-ΔN122-PG). The expression of ΔN122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated β-catenin. However, if expressed in β-catenin-null epidermis, ΔN122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for β-catenin in its signaling functions in vivo and the phenotype observed in K5-ΔN122-PG mouse skin must be due to the aberrant activation of β-catenin signaling. On the other hand, the expression of ΔN122-PG in β-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation.
机译:β-catenin和plakoglobin均可在体外刺激Lef / Tcf靶基因的表达。已知β-连环蛋白与Lef / Tcf因子缔合并直接参与体内反式激活,而对珠蛋白在转录调控中的作用的研究较少。为了分析体内珠蛋白珠蛋白的功能,我们生成了在表皮N端截短的珠蛋白珠蛋白(ΔN122-PG)中表达的缺乏糖原合酶激酶3β磷酸化位点的转基因小鼠,因此具有抗降解的能力(转基因株系K5-ΔN122-PG)。 ΔN122-PG的表达导致其他毛发细菌,增生的毛囊和无创性毛囊肿瘤的形成,这种表型让人联想到由N末端截短的β-catenin的表达所诱导的表型。但是,如果在无β-catenin的表皮中表达,则ΔN122-PG不会诱导新的毛囊细菌和毛囊肿瘤。因此,ΔN122-PG在体内的信号传导功能中不能替代β-catenin,并且在K5-ΔN122-PG小鼠皮肤中观察到的表型必须归因于β-catenin信号传导的异常激活。另一方面,ΔN122-PG在无β-catenin的皮肤中的表达显着提高了突变小鼠的存活率,挽救了分化,并限制了小孔间表皮的过度增殖,这表明铂珠蛋白可能参与了细胞内信号转导事件。对于表皮分化至关重要。

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