Lefebvre Véronique, Dumitriu Bogdan, Penzo-Méndez Alfredo, Han Yu, Pallavi Bhattaram
Department of Cell Biology, Lerner Research Institute and Orthopaedic Research Center, Cleveland Clinic, 9500 Euclid Avenue (NC10), Cleveland, OH 44195, USA.
Int J Biochem Cell Biol. 2007;39(12):2195-214. doi: 10.1016/j.biocel.2007.05.019. Epub 2007 Jun 6.
Maintain stemness, commit to a specific lineage, differentiate, proliferate, or die. These are essential decisions that every cell is constantly challenged to make in multi-cellular organisms to ensure proper development, adult maintenance, and adaptability. SRY-related high-mobility-group box (Sox) transcription factors have emerged in the animal kingdom to help cells effect such decisions. They are encoded by 20 genes in humans and mice. They share a highly conserved high-mobility-group box domain that was originally identified in SRY, the sex-determining gene on the Y chromosome, and that has derived from a canonical high-mobility-group domain characteristic of chromatin-associated proteins. The high-mobility-group box domain binds DNA in the minor groove and increases its DNA binding affinity and specificity by interacting with many types of transcription factors. It also bends DNA and may thereby confer on Sox proteins a unique and critical role in the assembly of transcriptional enhanceosomes. Sox proteins fall into eight groups. Most feature a transactivation or transrepression domain and thereby also act as typical transcription factors. Each gene has distinct expression pattern and molecular properties, often redundant with those in the same group and overlapping with those in other groups. As a whole the Sox family controls cell fate and differentiation in a multitude of processes, such as male differentiation, stemness, neurogenesis, and skeletogenesis. We review their specific molecular properties and in vivo roles, stress recent advances in the field, and suggest directions for future investigations.
维持干性、定向分化为特定谱系、分化、增殖或死亡。在多细胞生物中，每个细胞都不断面临着做出这些至关重要的决定，以确保正常发育、成年期维持和适应性。与SRY相关的高迁移率族盒（Sox）转录因子在动物界中出现，帮助细胞做出此类决定。它们在人类和小鼠中由20个基因编码。它们共享一个高度保守的高迁移率族盒结构域，该结构域最初在Y染色体上的性别决定基因SRY中被鉴定出来，并且源自染色质相关蛋白特有的典型高迁移率族结构域。高迁移率族盒结构域在小沟中结合DNA，并通过与多种类型的转录因子相互作用来增加其DNA结合亲和力和特异性。它还能使DNA弯曲，从而可能赋予Sox蛋白在转录增强体组装中独特而关键的作用。Sox蛋白分为八组。大多数具有转录激活或转录抑制结构域，因此也作为典型的转录因子发挥作用。每个基因都有独特的表达模式和分子特性，通常与同一组中的基因冗余，与其他组中的基因重叠。总体而言，Sox家族在众多过程中控制细胞命运和分化，如雄性分化、干性、神经发生和骨骼发生。我们综述了它们的具体分子特性和体内作用，强调了该领域的最新进展，并提出了未来研究的方向。
