Eckert Dawid, Buhl Sandra, Weber Susanne, Jäger Richard, Schorle Hubert
Department of Developmental Pathology, Institute of Pathology, Sigmund-Freud Strasse 25, 53125 Bonn, Germany.
Genome Biol. 2005;6(13):246. doi: 10.1186/gb-2005-6-13-246. Epub 2005 Dec 28.
The AP-2 family of transcription factors consists of five different proteins in humans and mice: AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and AP-2epsilon. Frogs and fish have known orthologs of some but not all of these proteins, and homologs of the family are also found in protochordates, insects and nematodes. The proteins have a characteristic helix-span-helix motif at the carboxyl terminus, which, together with a central basic region, mediates dimerization and DNA binding. The amino terminus contains the transactivation domain. AP-2 proteins are first expressed in primitive ectoderm of invertebrates and vertebrates; in vertebrates, they are also expressed in the emerging neural-crest cells, and AP-2alpha-/- animals have impairments in neural-crest-derived facial structures. AP-2beta is indispensable for kidney development and AP-2gamma is necessary for the formation of trophectoderm cells shortly after implantation; AP-2alpha and AP-2gamma levels are elevated in human mammary carcinoma and seminoma. The general functions of the family appear to be the cell-type-specific stimulation of proliferation and the suppression of terminal differentiation during embryonic development.
转录因子AP-2家族在人类和小鼠中由五种不同的蛋白质组成:AP-2α、AP-2β、AP-2γ、AP-2δ和AP-2ε。青蛙和鱼类已知有部分但并非所有这些蛋白质的直系同源物,并且在原索动物、昆虫和线虫中也发现了该家族的同源物。这些蛋白质在羧基末端具有特征性的螺旋-跨度-螺旋基序,该基序与中央碱性区域一起介导二聚化和DNA结合。氨基末端包含反式激活结构域。AP-2蛋白首先在无脊椎动物和脊椎动物的原始外胚层中表达;在脊椎动物中,它们也在新兴的神经嵴细胞中表达,并且AP-2α基因敲除动物的神经嵴衍生面部结构存在缺陷。AP-2β对肾脏发育不可或缺,而AP-2γ对植入后不久滋养外胚层细胞的形成是必需的;AP-2α和AP-2γ在人类乳腺癌和精原细胞瘤中的水平升高。该家族的一般功能似乎是在胚胎发育过程中对细胞类型特异性的增殖刺激和终末分化的抑制。