P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Nucleus, DNA-Binding Proteins, Down-Regulation, Genetic Vectors, Mice, Molecular Sequence Data, NIH 3T3 Cells, Nerve Tissue Proteins, Oncogene Proteins, Peptide Fragments, Precipitin Tests, Protein Isoforms, Protein Precursors, Protein Structure, Tertiary, RNA, Messenger, Recombinant Proteins, Transfection, Transforming Growth Factor beta, Transforming Growth Factor beta1, Two-Hybrid System Techniques, Yeasts
Biochem. Biophys. Res. Commun.
Date: Mar. 19, 2004
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