dimerization of translationally controlled tumor protein is essential for its cytokine-like activity二聚翻译控制肿瘤蛋白对cytokine-like活动至关重要.pdfVIP

Dimerization of Translationally Controlled Tumor Protein Is Essential For Its Cytokine-Like Activity 1 1 1 1 2 3 Miyoung Kim , Hyun Jung Min , Hee Yeon Won , Heejin Park , Ji-Chul Lee , Heung-Woo Park , Junho 4 1 1 Chung , Eun Sook Hwang , Kyunglim Lee * 1 College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea, 2 Abxign, Seoul, Korea, 3 Division of Allergy and Clinical Immunology, Seoul National University Hospital, Seoul, Korea, 4 College of Medicine and Cancer Research Institute, Seoul National University, Seoul, Korea Abstract Background: Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). Methods and Findings: We found that only NH -terminal truncated, but not C-terminal truncated, TCTP shows cytokine 2 releasing activity compared to full-length TCTP. Interestingly, only NH2-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger flu