P311 binds to the latency associated protein and downregulates the expression of TGF-β1 and TGF-β2

详细信息    查看全文

• 作者：Paliwal ; Seema ; Shi ; Jinghua ; Dhru ; Urmil ; Zhou ; Yuanxiang ; Schuger ; Lucia
• 关键词：P311 ; TGF-β ; 1 ; TGF-β ; 2 ; TGF-β ; 3 ; LAP
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：March 19, 2004
• 年：2004
• 卷：315
• 期：4
• 页码：1104-1109
• 全文大小：1.57 M

文摘

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-β1 expression. Here we demonstrate that P311 downregulates not only TGF-β1, but also TGF-β2, expression, with no effect on TGF-β3. In addition, P311 interacts with TGF-β2 in a yeast two-hybrid system through a sequence encompassing part of the TGF-β latent associated protein (LAP) and part of mature TGF-β2. Coimmunoprecipitations demonstrated interaction between P311 and TGF-β1 and 2, but not TGF-β3. Additional coimmunoprecipitations after introducing LAP or mature TGF-β1 into cells demonstrated P311 binding to LAP, but not to mature TGF-β. 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-β isoforms. Finally, Smad3 activity was decreased in P311-expressing cells, but was corrected by exogenous TGF-β1 treatment, which also elevated TGF-β1 mRNA level. This suggested that P311 downregulates TGF-β1 and 2 in part by blocking TGF-β autoinduction.