The PRAME family of cancer testis antigens is essential for germline development and gametogenesis

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. Summary Sentence This review summarizes the current knowledge of the PRAME gene family and its function in germline development and gametogenesis.

Automated summary

The PRAME gene family, predominantly expressed in the testis and various tumors, plays multifaceted roles in germ cells as leucine rich repeat proteins localized in the nucleus and cytoplasm. These proteins act as transcriptional regulators in germline development, contributing to the maintenance of embryonic stem cell pluripotency, primordial germ cell development, and spermatogenic/oogenic cell differentiation/proliferation. They are also involved in organelles such as the rough endoplasmic reticulum, Golgi vesicle, germinal granules, centrioles, contributing to spermiogenesis. The PRAME gene family is essential for gametogenesis throughout the entire life cycle, with specific members in male or female germ cells, as well as shared molecular mechanisms with oncogenesis.