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Siah2 通过控制 ASPP2 的稳定性来调节紧密连接的完整性和细胞极性。

Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability.

机构信息

Signal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.

Research Division, Peter McCallum Cancer Centre, Melbourne, VIC, Australia.

出版信息

Oncogene. 2014 Apr 10;33(15):2004-10. doi: 10.1038/onc.2013.149. Epub 2013 May 6.

DOI:10.1038/onc.2013.149
PMID:23644657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3917971/
Abstract

Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity. The tumor suppressor protein ASPP (Apoptosis-Stimulating Proteins of p53) 2 has been implicated in control of cell adhesion and polarity through its effect on the PAR complex. Here we demonstrate that under hypoxic conditions, the ubiquitin ligase Siah (seven in absentia homolog)2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity. LC-MS/MS analysis identified ASPP2 and ASPP1 as Siah2-interacting proteins. Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2-mediated ubiquitination and proteasomal-dependent degradation. Inhibition of Siah2 expression increases ASPP2 levels and enhances ASPP2-dependent maintenance of tight junction (TJ) integrity, and polarized architecture in three dimensional (3D) organotypic culture. Conversely, increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture. In all, our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability.

摘要

细胞黏附和极性的改变与上皮细胞转化和转移能力密切相关。抑癌蛋白 ASPP（p53 凋亡刺激蛋白）2 可通过其对 PAR 复合物的影响来控制细胞黏附和极性，从而参与其中。在这里，我们证明在低氧条件下，泛素连接酶 Siah（seven in absentia homolog）2 通过控制 ASPP2 的可用性，对上皮细胞极性产生伴随影响。LC-MS/MS 分析鉴定出 ASPP2 和 AS

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/77de5813b4aa/nihms550101f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/17289e0210f9/nihms550101f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/2f6917b0816c/nihms550101f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/158f8279e227/nihms550101f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/77de5813b4aa/nihms550101f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/17289e0210f9/nihms550101f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/2f6917b0816c/nihms550101f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/158f8279e227/nihms550101f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba9/3917971/77de5813b4aa/nihms550101f4.jpg

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