Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poliovirus-encoded protease 3Cpro. 1997

P Yalamanchili, and U Datta, and A Dasgupta
Department of Microbiology and Immunology, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.

Host cell RNA polymerase II-mediated transcription is inhibited by poliovirus infection. Previous studies from our laboratory showed that activated transcription from a cyclic AMP-responsive element (CRE)-containing promoter was severely inhibited in extracts prepared from poliovirus-infected HeLa cells compared to those from mock-infected cells. Here we demonstrate that the CRE-binding protein, CREB, is specifically cleaved by the poliovirus-encoded protease 3Cpro both in vitro and in virus-infected cells. The proteolytic cleavage of CREB leads to a significant loss of its DNA binding as well as transcriptional activity. Additionally, we demonstrate that the phosphorylated, transcriptionally active form of CREB is cleaved by the viral protease in vitro. The results presented here suggest that a direct cleavage of CREB by the viral protease 3Cpro leads to inhibition of CREB-activated transcription in poliovirus-infected HeLa cells.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D011051 Poliomyelitis An acute infectious disease of humans, particularly children, caused by any of three serotypes of human poliovirus (POLIOVIRUS). Usually the infection is limited to the gastrointestinal tract and nasopharynx, and is often asymptomatic. The central nervous system, primarily the spinal cord, may be affected, leading to rapidly progressive paralysis, coarse FASCICULATION and hyporeflexia. Motor neurons are primarily affected. Encephalitis may also occur. The virus replicates in the nervous system, and may cause significant neuronal loss, most notably in the spinal cord. A rare related condition, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses. (From Adams et al., Principles of Neurology, 6th ed, pp764-5) Infantile Paralysis,Polio,Poliomyelitis, Nonpoliovirus,Poliomyelitis, Preparalytic,Encephalitis, Polio,Epidemic Acute Poliomyelitis,Polio Encephalitis,Poliomyelitis Infection,Poliomyelitis, Acute,Acute Poliomyelitis,Acute Poliomyelitis, Epidemic,Infection, Poliomyelitis,Infections, Poliomyelitis,Nonpoliovirus Poliomyelitis,Paralysis, Infantile,Poliomyelitides, Preparalytic,Poliomyelitis Infections,Poliomyelitis, Epidemic Acute,Polios,Preparalytic Poliomyelitis
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015967 Gene Expression Regulation, Viral Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses. Regulation of Gene Expression, Viral,Viral Gene Expression Regulation,Regulation, Gene Expression, Viral
D017362 Cyclic AMP Response Element-Binding Protein A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals. CREB Protein,DNA-Binding Protein, Cyclic AMP-Responsive,Cyclic AMP-Responsive DNA-Binding Protein,cAMP Response Element-Binding Protein,Cyclic AMP Responsive DNA Binding Protein,DNA Binding Protein, Cyclic AMP Responsive,cAMP Response Element Binding Protein
D017955 Poliovirus A species of ENTEROVIRUS which is the causal agent of POLIOMYELITIS in humans. Three serotypes (strains) exist. Transmission is by the fecal-oral route, pharyngeal secretions, or mechanical vector (flies). Vaccines with both inactivated and live attenuated virus have proven effective in immunizing against the infection. Brunhilde Virus,Human poliovirus 1,Human poliovirus 2,Human poliovirus 3,Lansing Virus,Leon Virus,Poliovirus Type 1,Poliovirus Type 2,Poliovirus Type 3,Polioviruses

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