A Novel Mammalian Transcription Factor Involved In Hsv G

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Abstract

The regulation of herpes simplex virus immediate early gene (IE) expression is governed by viral and cellular proteins that assemble a multiprotein transcription enhancer complex. The analysis of the protein components and the biochemical interactions provides a model for RNAPII directed transcription and identifies critical elements of the HSV IE gene regulatory mechanism. One such component, the cellular C1 factor, is a large and complex family of polypeptides derived by site-specific processing from a common precursor protein. This family of proteins functions to direct the assembly of the enhancer complex as well as to mediate the transcriptional activation potential of some of the associated polypeptides. Analyses of the aminoterminus of the C1 factor have indicated that this region (i) folds as a 7-bladed kelch domain; (ii) interacts with viral and cellular transcription factors/coactivators via a short common motif; and (iii) interacts with viral DNA replication proteins. These studies illustrate the roles of the C1 factor in both initial stages (IE transcription) and later stages (DNA replication) of the lytic cycle. A second domain consists of a series of 20 amino acid reiterations that are the sites of specific autocatalytic proteolysis to generate the C1 polypeptides. These reiterations also serve as specific surfaces for protein-protein interactions. Two C1-interacting proteins, exhibit distinct requirements and specificities for the C1 repeats, suggesting that processing regulates a subset of C1-protein interactions and functions.