Differential effect of ik3-1/cables on p53- and p73-induced cell death.
ik3-1/Cables is associated with cdk3 in self-replicating cells. In postmitotic neurons, it may serve as an adaptor molecule, functionally connecting c-abl and cdk5, and supporting neurite growth. Here we report that ik3-1 binds to p53 and p73 in vivo. Ectopically expressed ik3-1 potentiates p53-induced cell death but not p73-induced cell death in U2OS cells. On the contrary, coexpression of ik3-1-DeltaC, an ik3-1 deletion mutant lacking the C-terminal 139 [corrected] amino acids (corresponding to the cyclin box-homologous region), inhibits p73-induced cell death but not p53-induced cell death. ik3-1-DeltaC-mediated inhibition of p73-induced cell death are partially attenuated by overexpression of ik3-1. These data indicate that ik3-1 is not only a regulator for p53-induced cell death but also an essential regulator for p73-induced cell death, and ik3-1-DeltaC competes with ik3-1 only in p73-induced cell death. Furthermore, functional domains of p53 responsible for its interaction with ik3-1 are partially different from those of p73. In conclusion, we found that ik3-1, a putative component of cell cycle regulation, is functionally connected with p53 and p73, but in distinct fashions.
Tsuji
Keitaro
K
Department of Pharmacology, KEIO University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Mizumoto
Kiyohisa
K
Yamochi
Tadanori
T
Nishimoto
Ikuo
I
Matsuoka
Masaaki
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002453:Cell Cycle; D016923:Cell Death; D002460:Cell Line; D002469:Cell Separation; D016213:Cyclins / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays
C486568:CABLES1 protein, human; D002352:Carrier Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005982:Glutathione Transferase