PACT-PKR Pathway Transactivates the Tumor Suppressor RhoB through C/EBPbeta in Cancer Cells with High Akt Activity

ABSTRACT: Activation of the PI3K/Akt/mTOR pathway in cancers can occur through loss of PTEN. Transcriptional profiling of pathway inhibitors identified the tumor suppressor RhoB as a gene markedly upregulated by lipid-based Akt inhibitors (LBAI). Here, we demonstrate that the C/EBPbeta full-length isoform LAP is responsible for transcriptional induction through its binding site within the RhoB proximal promoter. LBAI strongly transactivate RhoB by switching translation of C/EBPbeta from the truncated isoform LIP to LAP via PACT-mediated PKR activation in cancer cells with high Akt activity. Unlike PTEN commonly mutated, endogenous RhoB tumor-suppressive activity can be reconstituted by restoring its expression, which was noninvasively monitored by a RhoB promoter-driven luciferase reporter in living

ORGANISM(S): Homo sapiens

SUBMITTER: Dennis Phillip 

PROVIDER: S-ECPF-GEOD-28993 | biostudies-other |

REPOSITORIES: biostudies-other