TGFbeta regulation of membrane mucin Muc4 via proteosome degradation.
TGFbeta regulation of membrane mucin Muc4 via proteosome degradation.
复制标题
通过蛋白体降解对膜粘蛋白MUC4的TGFBETA调节。
DOI：
10.1002/jcb.22177
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发表时间：
2009-07-01
影响因子：
4
通讯作者：
Carraway, Kermit L.
中科院分区：
文献类型：
--
作者：
Lomako, Wieslawa M.;Lomako, Joseph.;Soto, Pedro;Carraway, Coralie A. Carothers;Carraway, Kermit L.
Muc4是一种与上皮分化和肿瘤进展有关的异源二聚体膜粘蛋白。它由单个基因表达为300 kDa前体蛋白，在内质网中切割成两个亚基。我们以前的工作表明，Muc4受TGFβ调节，TGF β抑制前体切割。通过对Muc4转染的A375肿瘤细胞的研究，我们发现Muc4发生了蛋白体降解。蛋白酶体抑制剂延长前体的寿命，将Muc4分流到细胞质侵袭体中，增加与内质网伴侣钙连接蛋白和钙网蛋白相关的Muc4的水平，并增加泛素化Muc4的水平。最重要的是，蛋白体抑制剂抑制了TGFβ对Muc4表达的抑制。这些结果表明，TGFβ抑制前体裂解，将前体分流到蛋白体降解途径中的模型。因此，细胞已经进化出一种机制，使用糖蛋白的质量控制途径来控制所产生的蛋白质的量。
Muc4 is a heterodimeric membrane mucin implicated in epithelial differentiation and tumor progression. It is expressed from a single gene as a 300 kDa precursor protein which is cleaved in the endoplasmic reticulum to its two subunits. Our previous work has shown that Muc4 is regulated by TGFβ, which represses the precursor cleavage. Working with Muc4-transfected A375 tumor cells, we now show that Muc4 undergoes proteosomal degradation. Proteosome inhibitors prolong the life of the precursor, shunt the Muc4 into cytoplasmic aggresomes, increase the level of Muc4 associated with the endoplasmic reticulum chaperones calnexin and calreticulin and increase the levels of ubiquitinated Muc4. Most importantly, proteosome inhibitors repress the TGFβ inhibition of Muc4 expression. These results suggest a model in which TGFβ inhibits precursor cleavage, shunting the precursor into the proteosomal degradation pathway. Thus, the cells have evolved a mechanism to use the quality control pathway for glycoproteins to control the quantity of the protein produced.
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DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
4.8
作者：
Komatsu, M;Carraway, CAC;Carraway, KL
通讯作者：
Carraway, KL
影响因子：
8
作者：
Komatsu, M;Jepson, S;Carraway, KL
通讯作者：
Carraway, KL
影响因子：
4
作者：
SHENG, Z;VANDERPUYE, OA;CARRAWAY, KL
通讯作者：
CARRAWAY, KL
影响因子：
6.4
作者：
Price-Schiavi, SA;Jepson, S;Carraway, KL
通讯作者：
Carraway, KL