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TID1 is a human homolog of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2)tid and encodes two mitochondrial matrix localized splice variants of human Tid-1 designated hTid-1S and hTid-1L. These proteins are the conserved members of the DnaJ family of proteins which act as cochaperones for mitochondrial Hsp70. They contain a conserved tetrahedrical J domain which binds to Hsp70 chaperones and activates their ATPase activity. Expression of hTid-1L increases apoptosis induced by DNA damaging agents as mitomycin-C and TNF-a. A J-domain mutant of hTid-1L can dominantly suppress apoptosis and in sharp contrast the J-domain mutant of hTid-1S increases apoptosis. Expression of hTid-1S and hTid-1L affects cytochrome c release from the mitochondria and caspase 3 activation, while activation of caspase 8 is unaffected. It is strongly suggested that these two splice variants exert their anti- and pro- apoptotic effects through discrete substrates and activities. Hence the relative abundance of these proteins or their substrates may allow the mitochondria to dampen or enhance the apoptotic signals.
1200003J13Rik; 1810053A11Rik; C81173; DnaJ (Hsp40) homolog, subfamily A, member 3; DnaJ heat shock protein family (Hsp40) member A3; dnaJ homolog subfamily A member 3, mitochondrial; DnaJ protein Tid-1; Dnaja3; HCA57; Hepatocellular carcinoma-associated antigen 57; hTID-1; mTid-1; Tid1; Tid-1; Tid1l; Tumorous imaginal discs protein Tid56 homolog
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