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. 2009 Dec 24;5(12):e1000626. doi: 10.1371/journal.pcbi.1000626

Figure 2. DMSO signaling pathway.

Figure 2

DMSO upregulates the tumor suppressor protein PTEN [15] in HL-60 cells. This increase in PTEN expression and activity is brought about by the activation of NF-κB. PTEN is a lipid phosphatase that is located in the cytoplasm and one of its primary roles is to dephosphorylate PIP3, a product of PI3K. The upregulation of PTEN results in a perturbation of the PI3k/Akt pathway, specifically the reduction in Akt phosphorylation levels and hence decreasing the amount of activated Akt. Normally activated Akt leads to phosphorylation of FOXO3, a member of the forkhead transcription factor family and this sets off further pathways that promote cell survival. However, inactive FOXO3 is able to translocate to the nucleus where it acts as a transcription factor, binding to cis-DNA elements and causing an increase in the gene expression of p27 [16]. The p27 protein inhibits the cyclin-dependent kinase complex Cyclin E and CDK2 which controls the G1 to S phase transition.