YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level
YB-1 is a multifunctional protein overexpressed in many types of cancer. It is a crucial oncoprotein that regulates cancer cell progression and proliferation. Ubiquitously expressed in human cells, YB-1 protein functions are strictly dependent on its subcellular localization. In the cytoplasm, where...
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MDPI AG
2021-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/10/1551 |
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| author | Antonella Delicato Eleonora Montuori Tiziana Angrisano Alessandra Pollice Viola Calabrò |
| author_facet | Antonella Delicato Eleonora Montuori Tiziana Angrisano Alessandra Pollice Viola Calabrò |
| author_sort | Antonella Delicato |
| collection | DOAJ |
| description | YB-1 is a multifunctional protein overexpressed in many types of cancer. It is a crucial oncoprotein that regulates cancer cell progression and proliferation. Ubiquitously expressed in human cells, YB-1 protein functions are strictly dependent on its subcellular localization. In the cytoplasm, where YB-1 is primarily localized, it regulates mRNA translation and stability. However, in response to stress stimuli and activation of PI3K and RSK signaling, YB-1 moves to the nucleus acting as a prosurvival factor. YB-1 is reported to regulate many cellular signaling pathways in different types of malignancies. Furthermore, several observations also suggest that YB-1 is a sensor of oxidative stress and DNA damage. Here we show that YB-1 reduces PTEN intracellular levels thus leading to PI3K/Akt pathway activation. Remarkably, PTEN reduction mediated by YB-1 overexpression can be observed in human immortalized keratinocytes and HEK293T cells and cannot be reversed by proteasome inhibition. Real-time PCR data indicate that YB-1 silencing up-regulates the PTEN mRNA level. Collectively, these observations indicate that YB-1 negatively controls PTEN at the transcript level and its overexpression could confer survival and proliferative advantage to PTEN proficient cancer cells. |
| first_indexed | 2024-03-10T06:32:57Z |
| format | Article |
| id | doaj.art-9eaf10a8444c4daaa627c9505e76397d |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T06:32:57Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9eaf10a8444c4daaa627c9505e76397d2023-11-22T18:21:44ZengMDPI AGGenes2073-44252021-09-011210155110.3390/genes12101551YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein LevelAntonella Delicato0Eleonora Montuori1Tiziana Angrisano2Alessandra Pollice3Viola Calabrò4Department of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, ItalyYB-1 is a multifunctional protein overexpressed in many types of cancer. It is a crucial oncoprotein that regulates cancer cell progression and proliferation. Ubiquitously expressed in human cells, YB-1 protein functions are strictly dependent on its subcellular localization. In the cytoplasm, where YB-1 is primarily localized, it regulates mRNA translation and stability. However, in response to stress stimuli and activation of PI3K and RSK signaling, YB-1 moves to the nucleus acting as a prosurvival factor. YB-1 is reported to regulate many cellular signaling pathways in different types of malignancies. Furthermore, several observations also suggest that YB-1 is a sensor of oxidative stress and DNA damage. Here we show that YB-1 reduces PTEN intracellular levels thus leading to PI3K/Akt pathway activation. Remarkably, PTEN reduction mediated by YB-1 overexpression can be observed in human immortalized keratinocytes and HEK293T cells and cannot be reversed by proteasome inhibition. Real-time PCR data indicate that YB-1 silencing up-regulates the PTEN mRNA level. Collectively, these observations indicate that YB-1 negatively controls PTEN at the transcript level and its overexpression could confer survival and proliferative advantage to PTEN proficient cancer cells.https://www.mdpi.com/2073-4425/12/10/1551YB-1PTENcold-shock proteinsproteasomePI3K/Akt pathway |
| spellingShingle | Antonella Delicato Eleonora Montuori Tiziana Angrisano Alessandra Pollice Viola Calabrò YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level Genes YB-1 PTEN cold-shock proteins proteasome PI3K/Akt pathway |
| title | YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level |
| title_full | YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level |
| title_fullStr | YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level |
| title_full_unstemmed | YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level |
| title_short | YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level |
| title_sort | yb 1 oncoprotein controls pi3k akt pathway by reducing pten protein level |
| topic | YB-1 PTEN cold-shock proteins proteasome PI3K/Akt pathway |
| url | https://www.mdpi.com/2073-4425/12/10/1551 |
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