Molecular chaperones are of particular significance in these systems. Molecular chaperones belong to a large family of proteins that prevent protein aggregation and/or promote refolding of non-native proteins. They are ubiquitous in all 3 kingdoms, and many of them are highly conserved. Except for typical chaperones like DnaK, GroEL, and small heat shock proteins, many proteins with well-characterized non-chaperone activities have now been shown to possess chaperone activity. Examples include EF-G, EF-Tu, thioredoxin, protein disulphide isomerase, and ribosomes. These observations suggest that intracellular chaperones are widely distributed among diverse functional classes. In this study, we show that E. coli GreA has chaperone activity, as evidenced by both repression of aggregation and reactivation of denatured proteins. When overexpressed, GreA enhances the resistance of host cells to environmental perturbations. GreAexpression also suppresses temperature-sensitive phenotype of greA/greB double mutant by alleviating cellular aggregation. To the best of our knowledge, this may be the first report of a transcription factor that has chaperone function. We therefore propose that in addition to its function as a transcription factor, GreA may play a role in protein quality control in vivo. GreA, a well-studied transcription factor in prokaryotes, has been reported to participate in several transcription-related processes. However, there is little evidence to suggest that transcription factors also have chaperone properties. Here, we show that the transcriptional elongation factor GreA suppresses protein aggregation and promotes reactivation of denatured proteins, which provide evidence that GreA also has chaperone activity. Although the activity of GreA is not so effective as DnaK, concerning the small molecular size and its main function as a transcription factor, we propose that the chaperone activity is notable. The crystal structure of GreA from E. coli, determined in 1995, revealed that the surface of the molecule is negatively charged uniformly, while the opposite surface has some hydrophobic patches. The ANS-binding experiment also confirmed the hydrophobic nature of the GreA protein. It has been previously suggested that GreA hydrophobic patches may act as a binding surface for interaction with the RNA polymerase complex. However, the hydrophobic patch also serves as a characteristic for some chaperone proteins, and we therefore reasoned that GreA may also utilize the hydrophobic patches for chaperone-like activity. Interestingly, as temperature was elevated, the hydrophobicity of GreA moderately increased while the secondary structure changed very Torin 1 abmole slightly. We propose that because of the high hydrophilicity of GreA, a slight increase in the hydrophobicity may not be severe enough to result in GreA unfolding, rather, it may provide more interacting surfaces for interaction with client proteins. Distinct from many other molecular chaperones, the binding capacity of GreA to the denatured substrates is very weak. Indeed, no obvious chaperone-substrate complexes were detected. This characteristic is similar to that of E. coli proteins of the thioredoxin family, namely, Trx, and YbbN, which have been reported to promote the refolding of denatured substrates but do not preferentially bind unfolded proteins. Although little sequence homology was observed between GreA and thioredoxins.