Advances in research on unphosphorylated STAT3: A review

Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, is a pivotal player in multiple cellular processes including proliferation, migration, differentiation, angiogenesis, programmed cell death, inflammatory response, and immune activation. As a transcription factor, the regulation of STAT3 activity is incredibly complicated as it is implicated signaling pathways in many distinct types of cells and under a diverse array of conditions. The activation of STAT3 commonly depends on the phosphorylation of specific residues in response to numerous growth factors and cytokines. With the discovery of STAT3 mediating gene expression in the absence of tyrosine/serine phosphorylation, a growing number of investigations related to unphosphorylated signal transducer and activator of transcription 3 (U-STAT3) demonstrated that U-STAT3 possess distinct features in regulation of gene expression. Herein, we summarize the current research progress in the roles of U-STAT3 in transcription and try to provide a basis for better understanding the complicated STAT3 activity regulation and its diverse functions.