Putting human Tid-1 in context: an insight into its role in the cell and in different disease states

Tumorous imaginal disc 1 (hTid-1) or DnaJ homolog subfamily A member 3 (DNAJA3), is a part of the heat shock protein (Hsp) 40 family and is predominantly found to reside in the mitochondria. hTid-1 has two mRNA splicing variants, hTid-1S and hTid-1L of 40 and 43 kDa respectively in the cytosol which are later processed upon import into the mitochondrial matrix. hTid-1 protein is a part of the DnaJ family of proteins which are co-chaperones and specificity factors for DnaK proteins of the Hsp70 family, and bind to Hsp70, thereby activating its ATPase activity. hTid-1 has been found to be critical for a lot of important cellular processes such as proliferation, differentiation, growth, survival, senescence, apoptosis, and movement and plays key roles in the embryo and skeletal muscle development.

hTid-1 participates in several protein-protein interactions in the cell, which mediate different processes such as proteasomal degradation and autophagy of the interacting protein partners. hTid-1 also functions as a co-chaperone and participates in interactions with several different viral oncoproteins. hTid-1 also plays a critical role in different human diseases such as different cancers, cardiomyopathies, and neurodegenerative disorders.

This review article is the first of its kind presenting consolidated information on the research findings of hTid-1 to date. This review suggests that the current knowledge of the role of hTid-1 in disorders like cancers, cardiomyopathies, and neurodegenerative diseases can be correlated with the findings of its protein-protein interactions that can provide a deep insight into the pathways by which hTid-1 affects disease pathogenesis and it can be stated that hTid-1 may serve as an important therapeutic target for these disorders. Video Abstract.