ZNF692, a novel nucleolar regulator in cancer

Abstract

Nucleolar function and ribosome biogenesis are essential for protein synthesis and cellular growth. Therefore, aberrant increase in nucleolar size and number are hallmarks of many cancers and have been associated with poor prognosis; nucleolar size is one of the most frequently used parameters by pathologists to grade solid tumors. While basic components and general molecular functions of the nucleolus have been studied, fundamental information on the mechanisms and molecules involved in the increased nucleolar size and activity specifically in cancer cells is missing. In an unbiased screen designed to identify growth promoting pathways in MYC‐transformed cells, our lab identified a novel and critical nucleolar regulator, the Zinc finger protein 692 (ZNF692) (manuscript in preparation). Our data has shown that ZNF692 downregulation interferes with protein synthesis and nucleolar function, and overexpression promotes nucleolar activity and protein synthesis. Moreover, we found that ZNF692 expression is dramatically increased in nearly all solid tumors deposited in the TGCA and is correlated with poor patient outcome. On a molecular level, our lab has shown that ZNF692 might play a role in rRNA processing. Through this project, we have unexpectedly discovered that ZNF692 is likely to coordinate cellular and mitochondrial ribosome production to fulfill the needs for rapid cell proliferation. This project aims to define understudied mechanisms and key regulators of increased ribosome biogenesis in cancer cells and could become the basis for the development of novel and unexplored approaches to alter nucleolar activity specifically in solid tumors.