Cornelia M. Gorman

The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins.

We have examined the effect of adenovirus E1 proteins on expression from the immediate early (IE) region of the human cytomegalovirus (HCMV). The major immediate early promoter, responsive to trans-activation during the HCMV lifecycle, is also responsive to E1 a protein encoded by the 13 S message. E1a proteins inhibit SV40 expression through the mechanism of enhancer repression; however, the presence of E1a proteins did not inhibit expression of the IE region of HCMV. The ability of trans-activate the major IE promoter in the presence of a strong enhancer suggests adenovirus can activate transcription of HCMV upon coinfection. E1b proteins increased levels of steady state mRNA transcribed from the IE region. Increases in expression due to E1a and E1b proteins were additive. These results suggest that adenovirus early expression can activate quiescent HCMV sequences.

Prohormone Processing Enzymes and Protein Production

There are two general classes of proteins synthesized by the cell: the group of cytosolic proteins (including proteins of the nucleus and mitochondria) and the secretory proteins. The secretory proteins generally undergo extensive posttranslational modification (glycosylation, fatty acylation, proteolysis, and so on) as they travel though the endoplasmic reticulum (ER) and Golgi apparatus (summarized in Fig. 6.1) (reviewed in 1). Proteins targeted to the secretory apparatus with final destinations outside of the cell are also subdivided into two groups: proteins that enter the default, or constitutive pathway, and those specifically sorted to the regulated pathway of secretion (2). Unlike the ubiquitous constitutive pathway, regulated secretion is restricted to certain cell types (endocrine and exocrine) and to specific kinds of proteins (e.g., certain prohormones and degradative enzymes, such as trypsin, and the like). Furthermore, an important feature that distinguishes the regulated from the constitutive pathway is the requirement for a specific extracellular signal before stored proteins within the coated secretory granules may be released into the external milieu of the cell. Proteins that are constitutively released do not have these restrictions.