| First Author | Paliwal S | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 315 |
| Issue | 4 | Pages | 1104-9 |
| PubMed ID | 14985127 | Mgi Jnum | J:88555 |
| Mgi Id | MGI:3034115 | Doi | 10.1016/j.bbrc.2004.01.171 |
| Citation | Paliwal S, et al. (2004) P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2. Biochem Biophys Res Commun 315(4):1104-9 |
| abstractText | P311 is an 8-kDa protein originally found in neurons and muscle. We recently showed that expression of P311 in NIH 3T3 cells induced a myofibroblast phenotype with low TGF-beta1 expression. Here we demonstrate that P311 downregulates not only TGF-beta1, but also TGF-beta2, expression, with no effect on TGF-beta3. In addition, P311 interacts with TGF-beta2 in a yeast two-hybrid system through a sequence encompassing part of the TGF-beta latent associated protein (LAP) and part of mature TGF-beta2. Coimmunoprecipitations demonstrated interaction between P311 and TGF-beta1 and 2, but not TGF-beta3. Additional coimmunoprecipitations after introducing LAP or mature TGF-beta1 into cells demonstrated P311 binding to LAP, but not to mature TGF-beta. P311 has a conserved PEST domain, which generally serves as a rapid degradation signal. Deletion of the PEST domain reversed the effect of P311 on TGF-beta isoforms. Finally, Smad3 activity was decreased in P311-expressing cells, but was corrected by exogenous TGF-beta1 treatment, which also elevated TGF-beta1 mRNA level. This suggested that P311 downregulates TGF-beta1 and 2 in part by blocking TGF-beta autoinduction. |
