Cold-inducible RNA-binding protein (CIRBP) (CIRBP)

Cold-inducible RNA-binding protein (CIRBP), also known as CIRP or hnRNP A18, is a versatile protein that functions as both an intracellular RNA chaperone and an extracellular damage-associated molecular pattern (DAMP) (UniProt P60568). Intracellularly, it is induced by various stressors such as cold shock, hypoxia, and UV radiation, where it regulates the stability and translation of target mRNAs involved in DNA repair, circadian rhythms, and cell survival (PubMed: 34558638). In response to severe stress or injury, CIRBP is secreted into the extracellular space (eCIRP), where it acts as a potent pro-inflammatory mediator by binding to receptors like TLR4/MD2 and TREM-1 (PubMed: 30691879). This extracellular activity drives the pathogenesis of conditions such as sepsis, hemorrhagic shock, and acute lung injury by triggering the release of inflammatory cytokines (PubMed: 24390302). In oncology, CIRBP exhibits a dual role, acting as either an oncogene or a tumor suppressor depending on the cancer type and cellular context (PubMed: 34558638). Therapeutic strategies currently under investigation include the use of peptide inhibitors like C23, which competitively blocks eCIRP binding to TLR4, and neutralizing antibodies to mitigate systemic inflammation (PubMed: 24390302). Monitoring serum eCIRP levels has also shown promise as a biomarker for disease severity and prognosis in inflammatory and ischemic disorders (PubMed: 30691879).

Other names

CIRPA18 hnRNPGlycine-rich RNA-binding protein CIRPhnRNP A18Testicular tissue protein Li 39

Competitive inhibition of extracellular CIRP binding to the TLR4/MD2 complex; Facilitation of phagocytic clearance of extracellular CIRP; Neutralization of extracellular CIRP