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PLoS One. 2010 May 27;5(5):e10859. doi: 10.1371/journal.pone.0010859.

miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics.

Author information

1
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.

Abstract

BACKGROUND:

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.

PRINCIPAL FINDINGS:

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.

CONCLUSIONS:

Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway.

PMID:
20523723
PMCID:
PMC2877705
DOI:
10.1371/journal.pone.0010859
[Indexed for MEDLINE]
Free PMC Article
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