Interleukin enhancer-binding factor 3 (ILF3) – survivin (BIRC5) promoter complex (ILF3–BIRC5 promoter complex)

The Interleukin enhancer-binding factor 3 (ILF3) – survivin (BIRC5) promoter complex is a transcriptional regulatory unit where the ILF3 protein (also known as NF90) binds to the promoter of the BIRC5 gene to drive the expression of survivin (Yamauchi et al., 2012, PubMed: 22710713). Survivin is a member of the inhibitor of apoptosis (IAP) family that is essential for cancer cell survival and mitotic regulation, making its expression a hallmark of malignancy (Nakahara et al., 2007, PubMed: 17671184). In many cancer types, ILF3 is upregulated and recruited to the survivin promoter, leading to the constitutive suppression of apoptosis (UniProt: Q12906). The small molecule sepantronium bromide (YM155) was identified as a potent inhibitor that specifically disrupts this complex, thereby reducing survivin mRNA and protein levels (Nakahara et al., 2011, PubMed: 21159643). Clinical development of drugs targeting this complex has focused on its role in solid tumors and lymphomas, though challenges include identifying patients with high expression of the necessary uptake transporters like SLC35F2 (Winter et al., 2014, PubMed: 24658034). This complex represents a unique target in oncology because it allows for the indirect inhibition of an undruggable protein like survivin by blocking its production at the genomic level. Disruption of the complex leads to the activation of caspases and the induction of programmed cell death in tumor cells. Research continues to explore the role of this complex in resistance to conventional chemotherapy and radiation.

Other names

NF90–survivin promoter complexILF3–BIRC5 promoter interactionNuclear factor 90–survivin promoter complexILF3–BIRC5 transcriptional complex

Inhibition of the binding of Interleukin enhancer-binding factor 3 (ILF3/NF90) to the survivin (BIRC5) promoter, thereby suppressing the transcription and expression of the anti-apoptotic protein survivin.