Regions essential for the interaction between Bcl-2 and SMN, the spinal muscular atrophy disease gene product |
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Authors: | Sato K Eguchi Y Kodama T S Tsujimoto Y |
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Institution: | Department of Medical Genetics, Biomedical Research Center (B8), Osaka University Graduate School of Medicine, and CREST, Japan Science and Technology Corp., 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. |
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Abstract: | The SMN gene is implicated in spinal muscular atrophy (SMA), and its product has been shown to interact with Bcl-2 protein to enhance its anti-apoptotic activity. In this study, we determined the regions that were essential for the interaction of Bcl-2 and SMN by co-immunoprecipitation of deletion mutants. Bcl-2 lacking its amino-terminal 20 amino acid residues or its carboxyl-terminal membrane-anchoring domain showed no or greatly reduced binding with SMN, respectively. However, Bcl-2 lacking other regions could still bind to SMN. Because Bcl-2 lacking the membrane-anchoring domain could bind to SMN in a yeast two-hybrid system, the amino-terminal region of Bcl-2 seems to be the most important domain for binding with SMN. A fragment of SMN encoded by exon 6 could bind to Bcl-2, but SMN lacking this region could not. From these results, we concluded that Bcl-2 and SMN proteins bound with each other at the amino-terminal region near the BH4 domain of Bcl-2 and the region encoded by exon 6 of SMN, both regions known to be important for their function. |
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