Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells.
Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells.
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DOI：
10.1371/journal.pone.0051497
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tyson-Capper AJ
中科院分区：
文献类型：
--
作者：
Gautrey HL;Tyson-Capper AJ
白血病调节基因Mcl-1（髓细胞白血病-1）的上调发生在不同的癌症类型中，并与癌症治疗的耐药性有关。众所周知，Mcl-1前mRNA经历选择性剪接事件以产生两种功能不同的蛋白质，Mcl-1 S（促凋亡）和Mcl-1 L（抗凋亡）;后一种同种型在包括乳腺癌和卵巢癌细胞在内的不同癌症中占主导地位。在本研究中，我们报告的RNA结合蛋白（RBP）和原癌基因SRSF 1（丝氨酸和丝氨酸丰富的剪接因子1）影响MCL-1在MCF-7和MDA-MB-231乳腺癌细胞和绒毛膜癌细胞的剪接;我们还首次表明，另一个RBP SRSF 5影响MCL-1在MCF-7细胞的剪接。此外，我们报告说，SRSF 1参与了Mcl-1调控的其他方面，通过RNAi敲低SRSF 1，导致MCF-7细胞中Mcl-1蛋白水平显著降低，但通过潜在地影响Mcl-1的蛋白稳定性和翻译，分别增加了MCF-7细胞中Mcl-1蛋白水平。这项研究的关键发现强调了不同癌细胞的细胞背景对SRSF 1等多功能RBP功能的重要性，并对靶向Mcl-1的治疗方法产生了影响。
Up-regulation of the apoptosis-regulatory gene Mcl-1 (myeloid cell leukemia-1) occurs in different cancer types and is linked with drug resistance to cancer therapies. It is well known that Mcl-1 pre-mRNA undergoes alternative splicing events to produce two functionally distinct proteins, Mcl-1S (pro-apoptotic) and Mcl-lL (anti-apoptotic); the latter isoform is predominant in different cancers including breast and ovarian cancer cells. In the present study we report that the RNA-binding protein (RBP) and proto-oncogene SRSF1 (serine and arginine-rich splicing factor 1) influences splicing of Mcl-1 in both MCF-7 and MDA-MB-231 breast cancer cells and JAR choriocarcinoma cells; we also show for the first time that another RBP SRSF5 affects splicing of Mcl-1 in the MCF-7 cells. Moreover, we report that SRSF1 is involved in other aspects of Mcl-1 regulation with knockdown of SRSF1, by RNAi, resulting in a significant decrease in Mcl-1 protein levels in MCF-7 cells but an increase in JAR cells, respectively, by potentially affecting protein stability and translation of Mcl-l. The key findings from this study highlight the importance of the cellular context of different cancer cells for the function of multifunctional RBPs like SRSF1 and have implications for therapeutic approaches employed to target Mcl-1.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
7.7
作者：
Grosso, Ana Rita;Martins, Sandra;Carmo-Fonseca, Maria
通讯作者：
Carmo-Fonseca, Maria
影响因子：
8
作者：
Mott, J. L.;Kobayashi, S.;Gores, G. J.
通讯作者：
Gores, G. J.
DOI：
10.1073/pnas.0801376105
发表时间：
2008-10-07
影响因子：
11.1
作者：
Karni, Rotem;Hippo, Yoshitaka;Krainer, Adrian R.
通讯作者：
Krainer, Adrian R.
影响因子：
4.8
作者：
Bingle, CD;Craig, RW;Whyte, MKB
通讯作者：
Whyte, MKB