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

The Nuclear Interleukin 1 receptor-like 1–Transcription factor Jun complex (Nuclear ST2–c-Jun complex) is a regulatory protein assembly located within the cell nucleus that plays a pivotal role in modulating inflammatory gene expression. While the transmembrane isoform of ST2 (ST2L) typically functions as the cell-surface receptor for Interleukin-33 (IL-33), the protein can also localize to the nucleus where it directly interacts with the DNA-binding domain of the transcription factor c-Jun (Takezako et al., 2006). This interaction serves to sequester c-Jun, preventing it from forming the active Activator Protein-1 (AP-1) complex and binding to promoter regions of pro-inflammatory cytokines such as IL-6 and IL-12 (Brint et al., 2002). By acting as a negative regulator of AP-1-mediated transcription, the nuclear ST2–c-Jun complex functions as an endogenous brake on the inflammatory response. Dysregulation of this complex is associated with various pathological states, including chronic asthma, pulmonary fibrosis, and cardiovascular diseases, where the balance of ST2 isoforms and their localization is disrupted (Griesenauer & Paczesny, 2017). Although no drugs currently target this specific nuclear interaction directly, several monoclonal antibodies, such as Astegolimab and Itepekimab, are in clinical development to inhibit the IL-33/ST2 axis (Rivera-Rodriguez et al., 2021). These therapies aim to treat Type 2 inflammatory diseases by blocking the upstream signaling that leads to ST2-mediated effects, including its nuclear regulatory functions.

Other names

Nuclear ST2–c-Jun complexIL1RL1–JUN complexNuclear ST2–AP-1 complexST2L–c-Jun complexNuclear ST2–c-Jun interaction

Inhibition of the IL-33/ST2 signaling pathway to modulate the availability of ST2 for nuclear translocation and subsequent transcriptional regulation of inflammatory genes.