The adenovirus E1a protein stimulates transcription of a wide variety of viral and cellular genes. It is shown here that E1a has the two functions characteristic of a typical cellular activator: one direct E1a to the promoter, perhaps by interacting with a DNA-bound protein, and the other, an activating region, enables the bound activator to stimulate transcription.

Background-Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events. Methods and Results-We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, nϭ16) or stable coronary artery disease (nϭ44). The platelet transcriptomes were analyzed and single-gene models constructed to identify candidate genes with differential expression. We validated 1 candidate gene product by performing a prospective, nested case-control study (nϭ255 case-control pairs) among apparently healthy women to assess the risk of future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) associated with baseline plasma levels of the candidate protein. Platelets isolated from STEMI and coronary artery disease patients contained 54 differentially expressed transcripts. The strongest discriminators of STEMI in the microarrays were CD69 (odds ratio 6.2, PϽ0.001) and myeloid-related protein-14 (MRP-14; odds ratio 3.3, Pϭ0.002). Plasma levels of MRP-8/14 heterodimer were higher in STEMI patients (17.0 versus 8.0 g/mL, PϽ0.001). In the validation study, the risk of a first cardiovascular event increased with each increasing quartile of MRP-8/14 (P trend Ͻ0.001) such that women with the highest levels had a 3.8-fold increase in risk of any vascular event (PϽ0.001).Risks were independent of standard risk factors and C-reactive protein. Conclusions-The

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The adenovirus E1a protein (E1a), a potent transcription activator, contains a transcriptional activating region. Compared with previously described cellular and viral activators, E1a's activating region has unusual structural properties. It seems that E1a's activating region interacts with a cellular target not required for the function of transcriptional activators with 'acidic' activating regions. By contrast, the target of an acidic activating region is required both by acidic activators and by E1a. It is proposed that the cellular target of E1a's activating region is an 'adaptor' that allows E1a to interact with the basic transcriptional machinery.