Akt3 is responsible for the survival and proliferation of embryonic stem cells
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway plays an important role in regulating cell proliferation, metabolism, and survival. However, the distinct roles of Akt isoforms (Akt1, Akt2, and Akt3) in pluripotent stem cell maintenance are not fully defined. Using mouse e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2017-06-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/6/6/850 |
| _version_ | 1819138967458545664 |
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| author | Ling Wang Delun Huang Zongliang Jiang Yan Luo Carol Norris Ming Zhang Xiuchun Tian Young Tang |
| author_facet | Ling Wang Delun Huang Zongliang Jiang Yan Luo Carol Norris Ming Zhang Xiuchun Tian Young Tang |
| author_sort | Ling Wang |
| collection | DOAJ |
| description | The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway plays an important role in regulating cell proliferation, metabolism, and survival. However, the distinct roles of Akt isoforms (Akt1, Akt2, and Akt3) in pluripotent stem cell maintenance are not fully defined. Using mouse embryonic stem cells (ESCs), we show that direct inhibition of Akt activity leads to ESC apoptosis. The Akt3, but not Akt1 or Akt2, activity specifically regulates this effect. Inhibiting Akt3 also leads to a cell cycle arrest at G1 phase. These regulatory roles of Akt3 are dependent on its kinase activity. Blocking the expression of Akt1 plus Akt2 in ESCs does not affect cell survival or proliferation, although blocking Akt1 aggravates the apoptotic effect induced by depletion of Akt3. We further show that blocking Akt3 in ESCs results in significant nuclear accumulation of p53, as well as the activation of its downstream targets, such as Mdm2, p21, and Fas. Inhibiting p53 and its downstream targets partially rescued the effects caused by Akt3-depletion. Our results revealed an Akt3 isoform-specific mechanism for ESC survival and proliferation involving the control of p53 activity. |
| first_indexed | 2024-12-22T11:15:11Z |
| format | Article |
| id | doaj.art-639fae16c44042cf9898c07f14e63a12 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-22T11:15:11Z |
| publishDate | 2017-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-639fae16c44042cf9898c07f14e63a122022-12-21T18:28:03ZengThe Company of BiologistsBiology Open2046-63902017-06-016685086110.1242/bio.024505024505Akt3 is responsible for the survival and proliferation of embryonic stem cellsLing Wang0Delun Huang1Zongliang Jiang2Yan Luo3Carol Norris4Ming Zhang5Xiuchun Tian6Young Tang7 Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA Center for Open Research Resources and Equipment, University of Connecticut, Storrs, CT 06269, USA Animal Reproduction Institute, Guangxi University, Nanning, 530004, People's Republic of China Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway plays an important role in regulating cell proliferation, metabolism, and survival. However, the distinct roles of Akt isoforms (Akt1, Akt2, and Akt3) in pluripotent stem cell maintenance are not fully defined. Using mouse embryonic stem cells (ESCs), we show that direct inhibition of Akt activity leads to ESC apoptosis. The Akt3, but not Akt1 or Akt2, activity specifically regulates this effect. Inhibiting Akt3 also leads to a cell cycle arrest at G1 phase. These regulatory roles of Akt3 are dependent on its kinase activity. Blocking the expression of Akt1 plus Akt2 in ESCs does not affect cell survival or proliferation, although blocking Akt1 aggravates the apoptotic effect induced by depletion of Akt3. We further show that blocking Akt3 in ESCs results in significant nuclear accumulation of p53, as well as the activation of its downstream targets, such as Mdm2, p21, and Fas. Inhibiting p53 and its downstream targets partially rescued the effects caused by Akt3-depletion. Our results revealed an Akt3 isoform-specific mechanism for ESC survival and proliferation involving the control of p53 activity.http://bio.biologists.org/content/6/6/850Akt3Embryonic stem cellsCell survivalCell cyclep53 |
| spellingShingle | Ling Wang Delun Huang Zongliang Jiang Yan Luo Carol Norris Ming Zhang Xiuchun Tian Young Tang Akt3 is responsible for the survival and proliferation of embryonic stem cells Biology Open Akt3 Embryonic stem cells Cell survival Cell cycle p53 |
| title | Akt3 is responsible for the survival and proliferation of embryonic stem cells |
| title_full | Akt3 is responsible for the survival and proliferation of embryonic stem cells |
| title_fullStr | Akt3 is responsible for the survival and proliferation of embryonic stem cells |
| title_full_unstemmed | Akt3 is responsible for the survival and proliferation of embryonic stem cells |
| title_short | Akt3 is responsible for the survival and proliferation of embryonic stem cells |
| title_sort | akt3 is responsible for the survival and proliferation of embryonic stem cells |
| topic | Akt3 Embryonic stem cells Cell survival Cell cycle p53 |
| url | http://bio.biologists.org/content/6/6/850 |
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