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前HB-EGF羧基末端片段的蛋白水解释放导致PLZF的核输出。

Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF.

作者信息

Nanba Daisuke, Mammoto Akiko, Hashimoto Koji, Higashiyama Shigeki

机构信息

Department of Medical Biochemistry, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan.

出版信息

J Cell Biol. 2003 Nov 10;163(3):489-502. doi: 10.1083/jcb.200303017. Epub 2003 Nov 3.

DOI:10.1083/jcb.200303017
PMID:14597771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2173632/
Abstract

Cleavage of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) via metalloprotease activation yields amino- and carboxy-terminal regions (HB-EGF and HB-EGF-C, respectively), with HB-EGF widely recognized as a key element of epidermal growth factor receptor transactivation in G protein-coupled receptor signaling. Here, we show a biological role of HB-EGF-C in cells. Subsequent to proteolytic cleavage of proHB-EGF, HB-EGF-C translocated from the plasma membrane into the nucleus. This translocation triggered nuclear export of the transcriptional repressor, promyelocytic leukemia zinc finger (PLZF), which we identify as an HB-EGF-C binding protein. Suppression of cyclin A and delayed entry of S-phase in cells expressing PLZF were reversed by the production of HB-EGF-C. These results indicate that released HB-EGF-C functions as an intracellular signal and coordinates cell cycle progression with HB-EGF.

摘要

通过金属蛋白酶激活作用切割膜锚定的肝素结合表皮生长因子样生长因子（proHB - EGF），产生氨基末端和羧基末端区域（分别为HB - EGF和HB - EGF - C），其中HB - EGF被广泛认为是G蛋白偶联受体信号传导中表皮生长因子受体反式激活的关键要素。在此，我们展示了HB - EGF - C在细胞中的生物学作用。proHB - EGF经蛋白水解切割后，HB - EGF - C从质膜转位至细胞核。这种转位触发了转录抑制因子早幼粒细胞白血病锌指蛋白（PLZF）的核输出，我们确定PLZF为一种HB - EGF - C结合蛋白。在表达PLZF的细胞中，细胞周期蛋白A的抑制以及S期进入的延迟通过产生HB - EGF - C得以逆转。这些结果表明，释放的HB - EGF - C作为一种细胞内信号发挥作用，并与HB - EGF协同调节细胞周期进程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/853ed4b4522a/200303017f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/ccc81ad67a49/200303017f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/7d4de95fdd98/200303017f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/c1d6c627ec41/200303017f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/1063ef7cd9ac/200303017f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/f7ca0f87e944/200303017f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/61508f151d74/200303017f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/2bc1584c4f75/200303017f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/fdaec83dec11/200303017f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/6b2481ee5ad8/200303017f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/853ed4b4522a/200303017f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/ccc81ad67a49/200303017f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/7d4de95fdd98/200303017f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/c1d6c627ec41/200303017f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/1063ef7cd9ac/200303017f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/f7ca0f87e944/200303017f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/61508f151d74/200303017f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/2bc1584c4f75/200303017f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/fdaec83dec11/200303017f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/6b2481ee5ad8/200303017f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cd/2173632/853ed4b4522a/200303017f10.jpg

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