| Human Tid-1 is a human orthologue of the Drosophila tumor suppressor lethal tumorous imaginal discs, and is a member of the DnaJ family of proteins that serve as co-chaperones to Hsp70 proteins. These proteins are characterized by a J domain, a highly conserved tetrahelical domain that binds to Hsp70 chaperones and activates their ATPase activity. Hsp70 and their associated chaperones mediate a variety of activities including the folding of newly synthesized polypeptides, the translocation of proteins across membranes and assembly of multimeric protein complexes. Two alternatively spliced variants exist for human Tid-1 ,designated hTID-1s and hTID-1L, both which contain the J domain, localize to the mitochondrial matrix, and co-immunoprecipitate with Hsp70. Expression of Tid-1L increases apoptosis induced by the DNA damaging agent mitomycin c (MMC) and by TNF-alpha, and that activity is dependent on its J domain. In contrast, expression of Tid-1S reduces apoptosis by these agents. Tid-1 orthologues are also found in mouse (mTid-1) and rat (rTid-1). The mouse orthologue was originally identified though its interaction with p120 GTPase-activating protein (GAP), raising the possiblity that Tid-1 helps regulates the confirmation, activity, or subcellular localization of GAP. |
