| First Author | Chen Y | Year | 2006 |
| Journal | Mamm Genome | Volume | 17 |
| Issue | 3 | Pages | 211-9 |
| PubMed ID | 16518688 | Mgi Jnum | J:106440 |
| Mgi Id | MGI:3618560 | Doi | 10.1007/s00335-005-0074-3 |
| Citation | Chen Y, et al. (2006) A novel mouse Smad4 mutation reduces protein stability and wild-type protein levels. Mamm Genome 17(3):211-9 |
| abstractText | Smad4 is a key signal transducer of the transforming growth factor-beta (TGF-beta) superfamily of growth factors that are critical regulators of embryonic patterning and adult tissue homeostasis. The biological activity of the TGF-beta signaling is tightly controlled at multiple levels, including the abundance of SMAD4 proteins. We previously recovered a novel allele of Smad4 in a gene-based screen in N-ethyl-N-nitrosourea (ENU)-mutagenized mouse embryonic stem cells. The mutation resulted in an unstable truncated protein that is degraded through proteasomal pathways. In the heterozygous state, this allele acts in a dominant negative fashion to reduce the wild-type protein level as well as signaling output. Biochemical characterization indicated that the truncated protein is able to form a complex with the wild-type protein, thus targeting it for proteasomal degradation as well. Phenotypic analyses of the heterozygous animals provided insight into the threshold requirement of Smad4-dependent signaling in vivo. |
