Single mage gene in the chicken genome encodes CMage, a protein with functional similarities to mammalian type II Mage proteins

Single mage gene in the chicken genome encodes CMage, a protein with functional similarities to mammalian type II Mage proteins
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DOI:
10.1152/physiolgenomics.00249.2006
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发表时间:
2007-07-18
影响因子:
4.6
通讯作者:
Maria Frade, Jose
Maria Frade, Jose
中科院分区:
生物学3区
文献类型:
--
作者:
Lopez-Sanchez, Noelia;Gonzalez-Fernandez, Zaira;Maria Frade, Jose

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在哺乳动物中,II型黑素瘤抗原(法师)蛋白家族由在不同组织(包括神经系统)中表达的至少10个密切相关的成员构成。这些蛋白质被认为调节细胞周期退出、神经元分化和凋亡。然而,对它们的具体功能的分析由于功能冗余而变得复杂。根据以往在硬骨鱼和果蝇中的研究,我们提出的证据表明,只有一个法师基因存在于原生生物,真菌,植物,线虫,昆虫和非哺乳类脊椎动物的基因组中。本研究鉴定了鸡法师基因,并克隆了编码鸡法师蛋白(CMage)的cDNA。CMage与II型法师蛋白家族具有密切的同源性,并且如先前对于II型法师蛋白Necdin和法师- G1所示,它可以与转录因子E2 F- 1相互作用。CMage在发育中的神经系统的特定区域中表达,包括视网膜神经节细胞层、脊髓的腹角和背根神经节,与神经营养因子受体p75(p75(NTR))在这些区域中的表达一致。我们发现,细胞内结构域的p75(NTR)可以与CMage和Necdin相互作用,从而防止后者的蛋白质的转录因子E2 F- 1的结合,并促进N1 E- 115分化神经元中的E2 F- 1的促凋亡活性。鸡基因组中单个法师基因的存在,以及CMage和Necdin之间的密切功能相似性,使得该物种成为进一步分析通过II型法师蛋白的信号转导的理想物种。
In mammals, the type II melanoma antigen ( Mage) protein family is constituted by at least 10 closely related members that are expressed in different tissues, including the nervous system. These proteins are believed to regulate cell cycle withdrawal, neuronal differentiation, and apoptosis. However, the analysis of their specific function has been complicated by functional redundancy. In accordance with previous studies in teleosts and Drosophila, we present evidence that only one mage gene exists in genomes from protists, fungi, plants, nematodes, insects, and nonmammalian vertebrates. We have identified the chicken mage gene and cloned the cDNA encoding the chick Mage protein ( CMage). CMage shares close homology with the type II Mage protein family, and, as previously shown for the type II Mage proteins Necdin and Mage- G1, it can interact with the transcription factor E2F- 1. CMage is expressed in specific regions of the developing nervous system including the retinal ganglion cell layer, the ventral horn of the spinal cord, and the dorsal root ganglia, coinciding with the expression of the neurotrophin receptor p75 ( p75(NTR)) in these regions. We show that the intracellular domain of p75(NTR) can interact with both CMage and Necdin, thus preventing the binding of the latter proteins to the transcription factor E2F- 1, and facilitating the proapoptotic activity of E2F- 1 in N1E- 115 differentiating neurons. The presence of a single mage gene in the chicken genome, together with the close functional resemblance between CMage and Necdin, makes this species ideal to further analyze signal transduction through type II Mage proteins.