The c-Myc proto-oncogene encodes a transcription factor that is essential for cell growth and proliferation and is broadly implicated in tumorigenesis. However, the biological functions required by c-Myc to induce oncogenesis remain elusive. Here we show that c-Myc has a direct role in the control of DNA replication. c-Myc interacts with the pre-replicative complex and localizes to early sites of DNA synthesis. Depletion of c-Myc from mammalian (human and mouse) cells as well as from Xenopus cell-free extracts, which are devoid of RNA transcription, demonstrates a non-transcriptional role for c-Myc in the initiation of DNA replication. Overexpression of c-Myc causes increased replication origin activity with subsequent DNA damage and checkpoint activation. These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and oncogenic functions.

SummaryWe have investigated the effect of metformin on the mechanisms of angiogenesis. We show that metformin, particularly in the context of obesity, inhibits angiogenesis in vivo yet shows a contradictory effect on angiogenesis-related genes and proteins that involve AMPK.

TS interaction with IL-1beta modulates PTEN activity though the ROS/Src/EGFR-p38MAPK pathway. PTEN deactivation is essential to increase VE-cadherin and beta-catenin p-Tyr and to disassemble VE-cadherin/beta-catenin membrane complexes, events that lead to accumulation of beta-catenin within the nucleus.