The herpes simplex virus immediate-early ubiquitin ligase ICP0 induces degradation of the ICP0 repressor protein E2FBP1. 2011

Yayoi Fukuyo, and Nobuo Horikoshi, and Alexander M Ishov, and Saul J Silverstein, and Takuma Nakajima
California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 220, San Francisco, California 94107, USA.

E2FBP1/hDRIL1, a DNA-binding A/T-rich interaction domain (ARID) family transcription factor, is expressed ubiquitously in human tissues and plays an essential role in maintaining the proliferation potential of passage-limited human fibroblasts by dissociating promyelocytic leukemia nuclear bodies (PML-NBs). This effect on PML-NBs is similar to that of viral immediate-early gene products, such as infected cellular protein 0 (ICP0) from human herpes simplex virus 1 (HSV-1), which also disrupts PML-NBs to override the intrinsic cellular defense. Here we report that E2FBP1 inhibits accumulation of ICP0 RNA and, at the same time, is degraded via ICP0's herpes ubiquitin ligase 2 (HUL-2) activity upon HSV-1 infection. These reciprocal regulatory roles of ICP0 and E2FBP1 are linked in an ARID-dependent fashion. Our results suggest that E2FBP1 functions as an intrinsic cellular defense factor in spite of its PML-NB dissociation function.

UI MeSH Term Description Entries
D012097 Repressor Proteins Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release. Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D044767 Ubiquitin-Protein Ligases A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes. Ubiquitin-Protein Ligase,E3 Ligase,E3 Ubiquitin Ligase,Ubiquitin Ligase E3,Ubiquitin-Protein Ligase E3,Ligase E3, Ubiquitin,Ligase E3, Ubiquitin-Protein,Ligase, E3,Ligase, E3 Ubiquitin,Ligase, Ubiquitin-Protein,Ligases, Ubiquitin-Protein,Ubiquitin Ligase, E3,Ubiquitin Protein Ligase,Ubiquitin Protein Ligase E3,Ubiquitin Protein Ligases
D054884 Host-Pathogen Interactions The interactions between a host and a pathogen, usually resulting in disease. Host Pathogen Interaction,Host-Pathogen Relations,Pathogen-Host Interaction,Pathogen-Host Interactions,Host Pathogen Interactions,Host Pathogen Relations,Host-Pathogen Interaction,Host-Pathogen Relation,Interaction, Host Pathogen,Interaction, Host-Pathogen,Interaction, Pathogen-Host,Interactions, Host Pathogen,Interactions, Host-Pathogen,Interactions, Pathogen-Host,Pathogen Host Interaction,Pathogen Host Interactions,Pathogen Interaction, Host,Pathogen Interactions, Host,Relation, Host-Pathogen,Relations, Host-Pathogen
D017874 Immediate-Early Proteins Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals. Proteins, Immediate-Early,Immediate Early Proteins,Proteins, Immediate Early
D018259 Herpesvirus 1, Human The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions. HSV-1,Herpes Simplex Virus 1,HHV-1,Herpes Simplex Virus Type 1,Herpesvirus 1 (alpha), Human,Human Herpesvirus 1
D037521 Virulence Factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486) Pathogenicity Factor,Pathogenicity Factors,Virulence Factor,Factor, Pathogenicity,Factor, Virulence,Factors, Pathogenicity,Factors, Virulence

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