Department of Animal Science, Center for Reproductive Biology and Health (CRBH), College of Agricultural Sciences, The Pennsylvania State University, University Park, PA, USA.
Biol Reprod. 2021 Aug 3;105(2):290-304. doi: 10.1093/biolre/ioab074.
Preferentially expressed antigen in melanoma (PRAME) belongs to a group of cancer/testis antigens that are predominately expressed in the testis and a variety of tumors, and are involved in immunity and reproduction. Much of the attention on PRAME has centered on cancer biology as PRAME is a prognostic biomarker for a wide range of cancers and a potential immunotherapeutic target. Less information is available about the PRAME family's function (s) during gametogenesis and in the overall reproduction process. Here, we review the current knowledge of the PRAME gene family and its function in germline development and gametogenesis. Members of the PRAME family are leucine rich repeat proteins, localized in nucleus and cytoplasm, with multifaceted roles in germ cells. As transcriptional regulators, the PRAME family proteins are involved in germline development, particularly in the maintenance of embryonic stem cell pluripotency, development of primordial germ cells, and differentiation/proliferation of spermatogenic and oogenic cells. The PRAME family proteins are also enriched in cytoplasmic organelles, such as rough endoplasmic reticulum, Golgi vesicle, germinal granules, centrioles, and play a role in the formation of the acrosome and sperm tail during spermiogenesis. The PRAME gene family remains transcriptionally active in the germline throughout the entire life cycle and is essential for gametogenesis, with some members specific to either male or female germ cells, while others are involved in both male and female gametogenesis. A potential molecular mechanism that underlies the function of PRAME, and is shared by gametogenesis and oncogenesis is also discussed.
黑色素瘤优先表达抗原 (PRAME) 属于一组癌症/睾丸抗原，主要在睾丸和多种肿瘤中表达，参与免疫和生殖。PRAME 的大部分关注点都集中在癌症生物学上，因为 PRAME 是广泛癌症的预后生物标志物，也是潜在的免疫治疗靶点。关于 PRAME 家族在配子发生和整个生殖过程中的功能知之甚少。在这里，我们回顾了 PRAME 基因家族及其在生殖细胞发生和配子发生中的功能的现有知识。PRAME 家族成员是富含亮氨酸重复的蛋白质，定位于细胞核和细胞质中，在生殖细胞中具有多方面的作用。作为转录调节剂，PRAME 家族蛋白参与生殖细胞的发育，特别是在维持胚胎干细胞多能性、原始生殖细胞的发育以及精子发生和卵母细胞的分化/增殖中。PRAME 家族蛋白也富含细胞质细胞器，如粗面内质网、高尔基小泡、生殖颗粒、中心粒，并在精子发生过程中参与顶体和精子尾部的形成。PRAME 基因家族在整个生命周期的生殖细胞中保持转录活性，对于配子发生至关重要，其中一些成员特异性地存在于雄性或雌性生殖细胞中，而其他成员则参与雄性和雌性配子发生。还讨论了一个潜在的分子机制，该机制是 PRAME 的功能基础，它与配子发生和肿瘤发生共享。
