Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells
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 (pr...
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| Format: | Online |
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Public Library of Science
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524227/ |
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pubmed-3524227 |
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pubmed-35242272013-01-02 Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells Gautrey, Hannah L. Tyson-Capper, Alison J. Research Article 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. Public Library of Science 2012-12-17 /pmc/articles/PMC3524227/ /pubmed/23284704 http://dx.doi.org/10.1371/journal.pone.0051497 Text en © 2012 Gautrey, Tyson-Capper http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Gautrey, Hannah L. Tyson-Capper, Alison J. |
| spellingShingle |
Gautrey, Hannah L. Tyson-Capper, Alison J. Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| author_facet |
Gautrey, Hannah L. Tyson-Capper, Alison J. |
| author_sort |
Gautrey, Hannah L. |
| title |
Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| title_short |
Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| title_full |
Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| title_fullStr |
Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| title_full_unstemmed |
Regulation of Mcl-1 by SRSF1 and SRSF5 in Cancer Cells |
| title_sort |
regulation of mcl-1 by srsf1 and srsf5 in cancer cells |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524227/ |
| _version_ |
1611941027175727104 |