Splice variants of mIAP1 have an enhanced ability to inhibit apoptosis.
Splice variants of mIAP1 have an enhanced ability to inhibit apoptosis.
复制标题
mIAP1 的剪接变体具有增强的抑制细胞凋亡的能力。
DOI：
10.1016/j.bbrc.2006.07.176
复制
发表时间：
2006
影响因子：
3.1
通讯作者：
Keri,RuthA
中科院分区：
文献类型：
--
作者：
Mosley,JonathanD;Keri,RuthA
c-IAP 1是凋亡抑制蛋白家族的成员。c-IAP 1的功能包括抑制细胞凋亡和激活NF-κB。在本文中，我们发现鼠c-IAP 1（mIAP 1）经历了可变剪接，产生了两种截短的蛋白质;一种缺乏CARD和RING结构域（mIAP 1-ΔCARDΔRING），另一种仅缺乏CARD结构域（mIAP 1-ΔCARD）。mIAP 1-ΔCARDΔRING mRNA在小鼠组织中的表达水平为全长mIAP 1（FL-mIAP 1）的2-3%，但其编码的蛋白质在培养细胞中的积累水平比FL-mIAP 1高50倍。该蛋白具有增强的抑制TNF-α诱导的细胞凋亡的能力，但不激活NF-κB报告基因。与mIAP 1-ΔCARDΔRING相比，mIAP 1-ΔCARD mRNA显示出明显的组织变异，范围为FL-mIAP 1 mRNA水平的5%至15%，并且其水平在退化期间在乳腺中增加。该亚型还具有增强的抗凋亡活性，但减少NF-κB活化。总之，mIAP 1是可变剪接的，产生具有不同功能特征的蛋白质亚型。
c-IAP1 is a member of the Inhibitor of Apoptosis protein family. Functions ascribed to c-IAP1 include inhibition of apoptosis and activation of NF-κB. Herein, we show that murine c-IAP1 (mIAP1) undergoes alterative splicing, generating two truncated proteins; one that lacks the CARD and RING domains (mIAP1-ΔCARDΔRING) and the other that lacks only the CARD domain (mIAP1-ΔCARD). mIAP1-ΔCARDΔRING mRNA is expressed at 2–3% of the levels of full-length mIAP1 (FL-mIAP1) in mouse tissues, yet it encodes a protein that accumulates at 50-fold higher levels than the FL-mIAP1 in cultured cells. This protein has an enhanced ability to inhibit Bax-induced apoptosis, but does not activate an NF-κB reporter. In contrast to mIAP1-ΔCARDΔRING, the mIAP1-ΔCARD mRNA displays distinct tissue variation, ranging from 5% to 15% of the FL-mIAP1 mRNA levels and its levels increase in the mammary gland during involution. This isoform also has enhanced anti-apoptotic activity, but diminished NF-κB activation. In summary, mIAP1 is alternatively spliced, generating protein isoforms with distinct functional characteristics.