Gene expression and transcription factor profiling reveal inhibition of transcription factor cAMP-response element-binding protein by gamma-herpesvirus replication and transcription activator.

Herpesvirus replication involves the expression of over 80 viral genes in a well ordered sequence, leading to the production of new virions. Viral genes expressed during the earliest phases of replication often regulate both viral and cellular genes. Therefore, they have the potential to bring about dramatic functional changes within the cell.

B cell terminal differentiation factor XBP-1 induces reactivation of Kaposi's sarcoma-associated herpesvirus.

The herpesvirus life cycle has two distinct phases: latency and lytic replication. The viral immediate early protein replication and transcription activator (RTA) plays a central role in mediating the balance between these two phases. Here, we demonstrate that a B cell terminal differentiation factor X-box binding protein 1 (XBP-1) can effectively initiates Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation by activating the RTA promoter, which results in the induction of other viral lytic transcripts.

Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication.

Identification of novel mammalian growth regulatory factors by genome-scale quantitative image analysis.

Functional profiling technologies using arrayed collections of genome-scale siRNA and cDNA arrayed libraries enable the comprehensive global analysis of gene function. However, the current repertoire of high-throughput detection methodologies has limited the scope of cellular phenotypes that can be studied. In this report, we describe the systematic identification of mammalian growth-regulatory factors achieved through the integration of automated microscopy, pattern recognition analysis, and cell-based functional genomics.

PDX1, a cellular homeoprotein, binds to and regulates the activity of human cytomegalovirus immediate early promoter.

Cellular homeoproteins have been shown to regulate the transcription of several viruses, including herpes simplex viruses, human papillomaviruses, and mouse mammary tumor viruses. Previous studies investigating the anti-viral mechanisms of several cyclin-dependent kinase inhibitors showed that the homeoproteins, pre B-cell leukemia transcription factor 1 (PBX1) and PBX-regulating protein-1 (PREP1), function as transcriptional activators of Moloney murine leukemia virus. Here, we examined the involvement of cellular homeoproteins in regulating the activity of the human cytomegalovirus immediate early (CMV IE) promoter.

Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery.

During the early phase of infection, the E1B-55K protein of adenovirus type 5 (Ad5) counters the E1A-induced stabilization of p53, whereas in the late phase, E1B-55K modulates the preferential nucleocytoplasmic transport and translation of the late viral mRNAs. The mechanism(s) by which E1B-55K performs these functions has not yet been clearly elucidated. In this study, we have taken a proteomics-based approach to identify and characterize novel E1B-55K-associated proteins.