Mendrysa S M, McElwee M K, Perry M E
Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, WI, Madison, USA.
Gene. 2001 Feb 7;264(1):139-46. doi: 10.1016/s0378-1119(00)00589-8.
The murine double minute 2 (mdm2) gene is essential for embryogenesis in mice that express the p53 tumor suppressor protein. Mdm2 levels must be regulated tightly because overexpression of mdm2 contributes to tumorigenesis. We investigated whether the 5' and 3' untranslated regions (UTRs) of murine mdm2 affect the expression of MDM2 proteins. Induction of mdm2 expression by p53 results in synthesis of an mdm2 mRNA with a short 5' UTR. The long 5' UTR increases internal initiation of translation of a minor MDM2 protein, p76(MDM2), without affecting the efficiency of translation of the full-length p90(MDM2). We discovered two alternative 3' untranslated regions in murine mdm2 mRNA expressed in the testis. The longer 3' UTR contains a consensus instability element, but mdm2 mRNAs containing the long and short 3' UTRs have comparable half-lives. The 3' UTRs do not affect either initiation codon use or translation efficiency. Thus, the murine 5' UTR, but not the 3'UTR, influences the ratio of the two MDM2 proteins but neither UTR affects MDM2 abundance significantly.
鼠双微体2（mdm2）基因对于表达p53肿瘤抑制蛋白的小鼠胚胎发育至关重要。必须严格调控mdm2的水平，因为mdm2的过表达会促进肿瘤发生。我们研究了鼠mdm2的5'和3'非翻译区（UTR）是否影响MDM2蛋白的表达。p53诱导mdm2表达会导致合成具有短5'UTR的mdm2 mRNA。长5'UTR增加了次要MDM2蛋白p76（MDM2）的内部翻译起始，而不影响全长p90（MDM2）的翻译效率。我们在睾丸中表达的鼠mdm2 mRNA中发现了两个可变的3'非翻译区。较长的3'UTR包含一个共有不稳定元件，但含有长和短3'UTR的mdm2 mRNA具有相当的半衰期。3'UTR既不影响起始密码子的使用也不影响翻译效率。因此，鼠5'UTR而非3'UTR影响两种MDM2蛋白的比例，但两个UTR均不显著影响MDM2的丰度。
