Tid1 is a Smad-binding protein that can modulate Smad7 activity in developing embryos.
In a search for binding partners to Smad8, we identified the chicken homologue of the mammalian Tid1 protein (cTid1), which is a regulator of apoptosis related to the Drosophila tumour suppressor Tid56. The cTid1 coding sequence is highly conserved with mammalian Tid1, including the DnaJ domain that interacts with Hsp70 (heat-shock protein 70). The cTid1 gene is widely expressed with transcripts enriched in the developing blood islands of the embryonic-yolk sac. We show that cTid1 can bind to other members of the Smad family and that highest binding activity occurs with the negative regulatory Smad7, through the conserved MH2 domain. This interaction can have functional relevance in vivo, since co-expression of Tid1 blocks the dorsalizing and BMP (bone morphogenetic protein)-dependent regulatory activity of Smad7 in developing Xenopus embryos. The finding that these proteins can interact suggests the potential for linking two important cell survival/apoptosis pathways.
Torregroza
Ingrid
I
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Evans
Todd
T
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001757:Blastomeres / Q000378:metabolism; D002460:Cell Line; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051906:Smad7 Protein / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism
D030161:Avian Proteins; D012333:RNA, Messenger; D051906:Smad7 Protein; C497809:Smad7 protein, Xenopus; D029867:Xenopus Proteins