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-1(S) (...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3524227?pdf=render |
| _version_ | 1811268712615903232 |
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| author | Hannah L Gautrey Alison J Tyson-Capper |
| author_facet | Hannah L Gautrey Alison J Tyson-Capper |
| author_sort | Hannah L Gautrey |
| collection | DOAJ |
| 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-1(S) (pro-apoptotic) and Mcl-l(L) (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. |
| first_indexed | 2024-04-12T21:27:55Z |
| format | Article |
| id | doaj.art-51688a7cb74c40e691f59ea41e2381d0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:27:55Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-51688a7cb74c40e691f59ea41e2381d02022-12-22T03:16:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5149710.1371/journal.pone.0051497Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells.Hannah L GautreyAlison J Tyson-CapperUp-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-1(S) (pro-apoptotic) and Mcl-l(L) (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.http://europepmc.org/articles/PMC3524227?pdf=render |
| spellingShingle | Hannah L Gautrey Alison J Tyson-Capper Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. PLoS ONE |
| title | 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_short | Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. |
| title_sort | regulation of mcl 1 by srsf1 and srsf5 in cancer cells |
| url | http://europepmc.org/articles/PMC3524227?pdf=render |
| work_keys_str_mv | AT hannahlgautrey regulationofmcl1bysrsf1andsrsf5incancercells AT alisonjtysoncapper regulationofmcl1bysrsf1andsrsf5incancercells |