| First Author | Wang GL | Year | 2004 |
| Journal | Genes Dev | Volume | 18 |
| Issue | 8 | Pages | 912-25 |
| PubMed ID | 15107404 | Mgi Jnum | J:219103 |
| Mgi Id | MGI:5619486 | Doi | 10.1101/gad.1183304 |
| Citation | Wang GL, et al. (2004) Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity. Genes Dev 18(8):912-25 |
| abstractText | Liver tumor cells arise from normal hepatocytes that escape negative control of proliferation. The transcription factor C/EBPalpha maintains quiescence of hepatocytes through two pathways: inhibition of cdks and repression of E2F. Nevertheless, liver tumors and cultured hepatoma cell lines proliferate in the presence of C/EBPalpha. In this paper, we present evidence that the activation of the PI3K/Akt pathway in liver tumor cells blocks the growth inhibitory activity of C/EBPalpha through the PP2A-mediated dephosphorylation of C/EBPalpha on Ser 193, leading to a failure of C/EBPalpha to interact with and inhibit cdks and E2F. Mutation of Ser 193 to Ala also abolishes the ability of C/EBPalpha to cause growth arrest because of a lack of interactions with cdk2 and E2F-Rb complexes. These data provide a molecular basis for the development of liver tumors in which the activation of PI3K/Akt pathway neutralizes C/EBPalpha growth inhibitory activity. |
