Cytoplasmic PML: From molecular regulation to biological functions

The tumor suppressor promyelocytic leukemia protein (PML) is predominantly localized in the nucleus, where it is essential for the formation and stabilization of the PML nuclear bodies (PML-NBs). PML-NBs are involved in the regulation of numerous cellular functions, such as tumorigenesis, DNA damage and antiviral responses. Despite its nuclear localization, a small portion of PML has been found in the cytoplasm. A number of studies recently demonstrated that the cytoplasmic PML (cPML) has diverse functions in many cellular processes including tumorigenesis, metabolism, antiviral responses, cell cycle regulation, and laminopothies. In this prospective, we will summarize the current viewpoints on the regulation and biological significance of cPML and discuss the important questions that still need to be further answered.