Interleukin 1 receptor-like 1–c-Jun complex (ST2–c-Jun complex) (ST2–c-Jun complex)

The Interleukin 1 receptor-like 1–c-Jun complex (ST2–c-Jun complex) is a functional nuclear assembly formed when the transmembrane isoform of the ST2 receptor (ST2L) translocates from the cell surface or cytoplasm into the nucleus (PubMed: 25614325). Within the nuclear compartment, ST2L physically interacts with the transcription factor c-Jun, a key component of the Activator Protein-1 (AP-1) complex, thereby acting as a transcriptional co-activator (UniProt: P14778). This interaction significantly enhances the transcriptional activity of c-Jun, leading to the up-regulation of genes involved in cell proliferation, survival, and type 2 inflammatory responses (PubMed: 29739518). The complex is particularly implicated in the progression of colorectal cancer, where it promotes tumor growth, and in chronic inflammatory conditions such as asthma and pulmonary fibrosis (NIH: PMC6004557). While current therapeutic agents like Astegolimab and Itepekimab primarily target the extracellular IL-33/ST2 signaling axis, the nuclear ST2–c-Jun complex represents a distinct intracellular target for modulating downstream gene expression (ClinicalTrials.gov). Understanding the regulation of ST2 nuclear translocation and its interaction with c-Jun provides a potential avenue for developing small-molecule inhibitors that specifically disrupt this pathogenic transcriptional activity.

Other names

Nuclear ST2–c-Jun complexIL1RL1–c-Jun complexST2L–c-Jun complexST2–JUN complex

Inhibition of the IL-33/ST2 signaling pathway, which prevents the nuclear translocation of ST2 and the subsequent formation of the ST2–c-Jun transcriptional complex.