DNA binding domain and subunit interactions of transcription factor IIIC revealed by dissection with poliovirus 3C protease. 1996

Y Shen, and M Igo, and P Yalamanchili, and A J Berk, and A Dasgupta
Molecular Biology Institute, University of California, Los Angeles, 90095-1570, USA.

Transcription factor IIIC (TFIIIC) is a general RNA polymerase III transcription factor that binds the B-box internal promotor element of tRNA genes and the complex of TFIIIA with a 5S rRNA gene. TFIIIC then directs the binding of TFIIIB to DNA upstream of the transcription start site. TFIIIB in turn directs RNA polymerase III binding and initiation. Human TFIIIC contains five different subunits. The 243-kDa alpha subunit can be specifically cross-linked to B-box DNA, but its sequence does not reveal a known DNA binding domain. During poliovirus infection, TFIIIC is cleaved and inactivated by the poliovirus-encoded 3C protease (3Cpro). Here we analyzed the cleavage of TFIIIC subunits by 3Cpro in vitro and during poliovirus infection of HeLa cells. Analyses of the DNA binding activities of the resulting subcomplexes indicated that an N-terminal 83-kDa domain of the alpha subunit associates with the beta subunit to generate the TFIIIC DNA binding domain. Cleavage with 3Cpro also generated an approximately 125-kDa C-terminal fragment of the alpha subunit which remained associated with the gamma and epsilon subunits.

UI MeSH Term Description Entries
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
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
D003546 Cysteine Endopeptidases ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
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
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
D000086042 3C Viral Proteases A class of cysteine proteases which play an essential role in VIRUS REPLICATION. They cleave precursor viral POLYPROTEINS to produce functional proteins and enzymes. In addition, they cleave certain host cell proteins such as EUKARYOTIC INITIATION FACTOR-4G. 3C Proteases,3C Proteinases,3C-like Viral Proteases,3Cpro Proteinases,Proteases, 3C,Proteases, 3C-like Viral,Proteinases, 3C,Viral Proteases, 3C-like
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
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

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