Biomaterial Database

Poliovirus protease 3C mediates cleavage of microtubule-associated protein 4. 1995

M Joachims, and K S Harris, and D Etchison

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160, USA.

Poliovirus infection results in a number of host cell changes, including specific alterations in cellular proteins. This study further characterizes the cleavage of a cytoskeletal protein, microtubule-associated protein 4 (MAP-4) and investigates the identity of the viral protease which mediates its cleavage. MAP-4 cleavage by poliovirus was previously identified using a monoclonal antibody (M. Joachims and D. Etchison, 1992, J. Virol. 66, 5997-5804). In this study, MAP-4 cleavage was found to occur in cells infected by only some picornaviruses, poliovirus and human rhinovirus 14. Infection by other types of viruses, vesicular stomatitis virus and adenovirus, or by other types of picornaviruses, encephalomyocarditis virus, did not result in MAP-4 cleavage. To determine the viral mediator of MAP-4 cleavage, the effects of purified poliovirus proteases on MAP-4 integrity were examined by immunoblot. When MAP-4 substrates were incubated with concentrations of poliovirus 2A that were more than sufficient to induce p220 cleavage, there was no effect on MAP-4. However, when MAP-4 substrates were incubated with purified 3C protease (3Cpro), cleavage products were detected that were identical in size to those generated in vivo in poliovirus-infected cells; the use of a mutant 3C protease did not result in MAP-4 cleavage. Cleavage of MAP-4 was also demonstrated with purified 3CDpro, and the in vitro cleavage kinetics were examined. Indirect immunofluorescence revealed that MAP-4 cleavage also correlated with a marked "collapse" of microtubules during late infection, indicating a possible relationship between 3Cpro-mediated MAP-4 cleavage and changes in the microtubule system of infected cells.

UI	MeSH Term	Description	Entries
D008869	Microtubule-Associated Proteins	High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.	Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D008870	Microtubules	Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.	Microtubule
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
D010849	Picornaviridae	A family of small RNA viruses comprising some important pathogens of humans and animals. Transmission usually occurs mechanically. There are nine genera: APHTHOVIRUS; CARDIOVIRUS; ENTEROVIRUS; ERBOVIRUS; HEPATOVIRUS; KOBUVIRUS; PARECHOVIRUS; RHINOVIRUS; and TESCHOVIRUS.	Avihepatovirus,Pasivirus,Picornaviruses,Rosavirus,Sapelovirus,Senecavirus,Sicinivirus,Tremovirus,Avihepatoviruses,Pasiviruses,Rosaviruses,Sapeloviruses,Senecaviruses,Siciniviruses,Tremoviruses
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.
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
D006868	Hydrolysis	The process of cleaving a chemical compound by the addition of a molecule of water.
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
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