miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics.
The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-05-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2877705?pdf=render |
| _version_ | 1818503769184272384 |
|---|---|
| author | Nadav Bar Rivka Dikstein |
| author_facet | Nadav Bar Rivka Dikstein |
| author_sort | Nadav Bar |
| collection | DOAJ |
| description | The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by AKT-mediated phosphorylation. PTEN activity is frequently lost in many types of cancer, leading to increased cell survival and cell cycle progression.Here we characterize the widely expressed miR-22 and report that miR-22 is a novel regulatory molecule in the PTEN/AKT pathway. miR-22 downregulates PTEN levels acting directly through a specific site on PTEN 3'UTR. Interestingly, miR-22 itself is upregulated by AKT, suggesting that miR-22 forms a feed-forward circuit in this pathway. Time-resolved live imaging of AKT-dependent FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal.Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway. |
| first_indexed | 2024-12-10T21:28:22Z |
| format | Article |
| id | doaj.art-a2f0c275ce154bba8a234b5bd8f15079 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T21:28:22Z |
| publishDate | 2010-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a2f0c275ce154bba8a234b5bd8f150792022-12-22T01:32:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1085910.1371/journal.pone.0010859miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics.Nadav BarRivka DiksteinThe tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by AKT-mediated phosphorylation. PTEN activity is frequently lost in many types of cancer, leading to increased cell survival and cell cycle progression.Here we characterize the widely expressed miR-22 and report that miR-22 is a novel regulatory molecule in the PTEN/AKT pathway. miR-22 downregulates PTEN levels acting directly through a specific site on PTEN 3'UTR. Interestingly, miR-22 itself is upregulated by AKT, suggesting that miR-22 forms a feed-forward circuit in this pathway. Time-resolved live imaging of AKT-dependent FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal.Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway.http://europepmc.org/articles/PMC2877705?pdf=render |
| spellingShingle | Nadav Bar Rivka Dikstein miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS ONE |
| title | miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. |
| title_full | miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. |
| title_fullStr | miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. |
| title_full_unstemmed | miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. |
| title_short | miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. |
| title_sort | mir 22 forms a regulatory loop in pten akt pathway and modulates signaling kinetics |
| url | http://europepmc.org/articles/PMC2877705?pdf=render |
| work_keys_str_mv | AT nadavbar mir22formsaregulatoryloopinptenaktpathwayandmodulatessignalingkinetics AT rivkadikstein mir22formsaregulatoryloopinptenaktpathwayandmodulatessignalingkinetics |