Transglutaminase 2 (TG2) is a ubiquitously expressed multi-functional member of the transglutaminase enzyme family. It has been implicated to have roles in many physiological and pathological processes such as differentiation, apoptosis, signal transduction, adhesion and migration, wound healing and inflammation. Previous studies revealed that TG2 has various intra- and extracellular interacting partners, which contribute to these processes. In this study, we identified a molecular co-chaperone, DNAJA1 as novel interacting partner of human TG2 using a GST pull down assay and subsequent mass spectrometry analysis and further confirmed this interaction via ELISA and SPR measurements. Interaction studies were also performed with domain variants of TG2 and results suggest that the catalytic core domain of TG2 is essential for the TG2-DNAJA1 interaction. Crosslinking activity was not essential for the interaction since DNAJA1 was also found to interact with the catalytically inactive form of TG2. Further, we have showed that DNAJA1 interacts with the open form of TG2 and regulates its transamidation activity both in vitro and in situ conditions. We also found that DNAJA1 is a glutamine donor substrate of TG2. Since DNAJA1 and TG2 are reported to regulate common pathological conditions such as neurodegenerative disorders and cancer, the findings in this paper open up possibilities to explore molecular mechanisms behind TG2 regulated functions.
- Transglutaminase 2
- core domain
- protein-protein interaction
- in situ crosslinking activity
- Copyright 2016 The Author(s)
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