Attempts to define the binding region through which TCTP dimerization occurs has resulted in an accumulation of inconsistent data, none of which explains the need for dimerization when present in serum. For example, a construct of TCTP truncated on its N-terminal 35 residues dimerizes in vitro, increases the secretion of IL-8 and GM-CSF from BEAS-2B cells, and enhances TCTP allergic response as measured by inhibition of IL-2 and release of IL-4 from CD4 + TH cells. In this case, it is proposed that dimerization of truncated TCTP is mediated by an intermolecular disulfide bridge provided by the C-terminal Cys172. However, whereas structural studies might provide indirect support for this model, the biochemical data seem conflicting. Accordingly, the solution structure of S. pombe TCTP, which on the basis of sequence homology defines the fold of the entire family,Picroside-I closely resembles features of the Mss4/Dss4 family of guanine nucleotide exchange factors. In this structure, both the N- and C-termini of TCTP are packed together as antiparallel b-sheets and, thus, it has been proposed that the N-terminus might interfere in the formation of disulfide bonds making its cleavage a requirement for dimerization to occur. However, the same group later found that dimerization of full-length TCTP, rather than the truncated form, is essential for the activation of TCTP-mediated allergic response. Because secretion of IL-8 was measured in vitro, the authors needed to artificially generate a dimeric form of TCTP for the study. This is an important detail when analyzed in the context of our studies since, we propose that dimerization of TCTP only occurs when high mM concentrations of heme are present,Coptisine-chloride as is the case in serum but not in in vitro experiments unless specifically added. Consistent with our results is the finding that dimeric full-length TCTP can be readily detectable in sera from atopic or atopic/asthmatic patients. Further support for a model of noncovalent dimerization of TCTP came from biochemical studies of secreted TCTP obtained from various extracellular environments.