No abstract

NCT01847274.

Overexpression of oncoprotein MDM2 has been found in a signi®cant number of human soft tissue tumors. In a subset of these tumors, overexpression is a result of enhanced translation of mdm2 mRNA. There are two transcripts from the mdm2 gene that di er only in their 5' leaders: a long form (L-mdm2) and a short form (Smdm2) that arise from the use of di erent promoters. Lmdm2 mRNA contains two upstream open reading frames (uORFs) and this mRNA was loaded with ribosomes ine ciently in comparison with S-mdm2. The 5' leader of L-mdm2 was su cient to transfer translational repression to a reporter gene and the two uORFs acted synergistically to achieve full suppression. In contrast, the 5' leader of S-mdm2 allowed e cient translation of an attached reporter gene in the tumor cells. These results are consistent with a model in which overexpression of MDM2 in certain tumors results from a change in mRNA structure due to a switch in promoter usage.

No abstract