Signal transducer and activator of transcription 3 (STAT3) (STAT3)

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that plays a pivotal role in mediating cellular responses to a variety of cytokines and growth factors, most notably the Interleukin-6 (IL-6) family [UniProt: P40763]. Upon phosphorylation by upstream kinases such as Janus kinases (JAKs), STAT3 undergoes dimerization through its SH2 domain and translocates to the nucleus to regulate the expression of genes involved in cell survival, proliferation, and immune evasion [PubMed: 28522731]. While its activity is tightly regulated in normal cells, STAT3 is constitutively activated in many human cancers, where it acts as a potent oncogene by promoting tumor growth and maintaining an immunosuppressive microenvironment [PubMed: 30206144]. In addition to oncology, STAT3 is implicated in inflammatory and autoimmune disorders, as well as genetic conditions like Hyper-IgE syndrome [PubMed: 25145938]. Current therapeutic strategies focus on small molecules that block dimerization, antisense oligonucleotides that reduce STAT3 expression, and inhibitors of the upstream JAK/STAT pathway [PubMed: 31221757].

Other names

Acute-phase response factorAPRFTranscription factor L12HIESADMIO

Inhibition of the SH2 domain to prevent dimerization; antisense-mediated degradation of mRNA to reduce protein levels; inhibition of the DNA-binding domain to prevent transcriptional activity.