Interaction between IGFBP-5 and TNFR1

Abstract

Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent KD of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.

Insulin-Like Growth Factor Binding Protein 5—A Probable Target of Kidney Renal Papillary Renal Cell Carcinoma

“…In addition to VEGFA and TGF- β , TNF-α is another important cytokine correlated with IGFBP5, although TNF-α expression and survival prognosis were not significant different between KIRP patients and controls. There has been reported that IGFBP-5 inhibits TNF-α by competitively binding to TNFR1 [24, 25]. We hypothesize that downregulated IGFBP5 expression might release the binding domain of TNFR1 to restore apoptosis induced by TNF-α in cancer cells.…”