Cleavage of transcriptional activator Oct-1 by poliovirus encoded protease 3Cpro.

In HeLa cells, RNA polymerase II mediated transcription is severely inhibited by poliovirus infection. Both basal and activated transcription are affected to bring about a complete shutoff of host cell transcription. We demonstrate here that the octamer binding transcription factor, Oct-1, is cleaved in HeLa cells infected with poliovirus. Incubation of Oct-1 with the purified, recombinant 3Cpro results in the generation of the cleaved Oct-1 product seen in virus infected cells. Poliovirus infection leads to the formation of altered Oct-1 DNA complexes that can also be generated by incubation of Oct-1 with purified 3Cpro. We also show that Oct-1 cleaved by 3Cpro loses its ability to inhibit transcriptional activation by the SV40 B enhancer. These results suggest that cleavage of Oct-1 in poliovirus infected cells leads to the loss of its activity.

[1]  M. Wintzerith,et al.  Multiple sequence motifs are involved in SV40 enhancer function. , 1986, The EMBO journal.

[2]  M. Ares,et al.  Human U2 small nuclear RNA genes contain an upstream enhancer. , 1986, The EMBO journal.

[3]  W. Herr,et al.  Activation of the U2 snRNA promoter by the octamer motif defines a new class of RNA polymerase II enhancer elements. , 1988, Genes & development.

[4]  E. Wimmer,et al.  Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus. , 1991, The EMBO journal.

[5]  E. Wimmer,et al.  Infection of HeLa cells with poliovirus results in modification of a complex that binds to the rRNA promoter , 1992, Journal of virology.

[6]  D. Baltimore,et al.  Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement for mammalian transcription factor IID. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Reinberg,et al.  Factors involved in specific transcription by mammalian RNA polymerase II: purification and analysis of transcription factor IIA and identification of transcription factor IIJ , 1992, Molecular and cellular biology.

[8]  P. Yalamanchili,et al.  Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poliovirus-encoded protease 3Cpro , 1997, Journal of virology.

[9]  S. Kliewer,et al.  An RNA polymerase II transcription factor inactivated in poliovirus-infected cells copurifies with transcription factor TFIID , 1988, Molecular and cellular biology.

[10]  A. Berk,et al.  Direct cleavage of human TATA-binding protein by poliovirus protease 3C in vivo and in vitro , 1993, Molecular and cellular biology.

[11]  P. Sharp,et al.  Inhibition of transcription factor activity by poliovirus , 1981, Cell.

[12]  B. Semler,et al.  Site-directed mutagenesis of proteinase 3C results in a poliovirus deficient in synthesis of viral RNA polymerase , 1987, Journal of virology.

[13]  A. Dasgupta,et al.  A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells , 1990, Molecular and cellular biology.

[14]  J. Jiricny,et al.  An enhancer-like sequence within the Xenopus U2 gene promoter facilitates the formation of stable transcription complexes , 1985, Nature.

[15]  N. Heintz,et al.  Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. , 1988, Genes & development.

[16]  R. Roeder,et al.  Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. , 1983, Nucleic acids research.

[17]  W. Herr,et al.  Discrete elements within the SV40 enhancer region display different cell‐specific enhancer activities. , 1987, The EMBO journal.

[18]  D. Reinberg,et al.  Factors involved in specific transcription by mammalian RNA polymerase II. Purification and functional analysis of initiation factors IIB and IIE. , 1987, The Journal of biological chemistry.

[19]  R. Burgess,et al.  Synthesis of human U1 RNA. II. Identification of two regions of the promoter essential for transcription initiation at position +1. , 1984, The Journal of biological chemistry.

[20]  R. Burgess,et al.  Transcription of a gene for human U1 small nuclear RNA , 1982, Cell.

[21]  C. Lawrence,et al.  Encephalomyocarditis Virus Infection of Mouse Plasmacytoma Cells II. Effect on Host RNA Synthesis and RNA Polymerases , 1974, Journal of virology.

[22]  D. Baltimore,et al.  The “initiator” as a transcription control element , 1989, Cell.

[23]  B. Semler,et al.  Picornavirus protein processing--enzymes, substrates, and genetic regulation. , 1990, Current topics in microbiology and immunology.

[24]  E. Wimmer,et al.  Inhibition of basal transcription by poliovirus: a virus- encoded protease (3Cpro) inhibits formation of TBP-TATA box complex in vitro , 1996, Journal of virology.

[25]  D. Reinberg,et al.  Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH. , 1992, The Journal of biological chemistry.

[26]  M. Vigneron,et al.  In vitro binding of cell‐specific and ubiquitous nuclear proteins to the octamer motif of the SV40 enhancer and related motifs present in other promoters and enhancers. , 1987, The EMBO journal.

[27]  E. Penhoet,et al.  Cellular RNA synthesis in normal and mengovirus-infected L-929 cells. , 1978, The Journal of biological chemistry.

[28]  R. Burgess,et al.  Functional elements of the human U1 RNA promoter. Identification of five separate regions required for efficient transcription and template competition. , 1987, The Journal of biological chemistry.

[29]  E. G. Jensen,et al.  The differential inhibitory effect of α‐amanitin on the synthesis of low molecular weight RNA components in BHK cells , 1978, FEBS letters.

[30]  Robert Tjian,et al.  Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins , 1985, Nature.

[31]  R. Tjian,et al.  Structure and functional properties of human general transcription factor IIE , 1991, Nature.

[32]  D. Reinberg,et al.  Factors involved in specific transcription in mammalian RNA polymerase II. Functional analysis of initiation factors IIA and IID and identification of a new factor operating at sequences downstream of the initiation site. , 1987, The Journal of biological chemistry.

[33]  R. Cortese,et al.  Transcription signals in embryonic Xenopus laevis U1 RNA genes. , 1985, The EMBO journal.

[34]  A. Dasgupta Purification of host factor required for in vitro transcription of poliovirus RNA. , 1983, Virology.

[35]  Luis Carrasco,et al.  Degradation of cellular proteins during poliovirus infection: studies by two-dimensional gel electrophoresis , 1989, Journal of virology.

[36]  R. Harvey,et al.  Independently evolving chicken histone H2B genes: identification of a ubiquitous H2B-specific 5' element. , 1982, Nucleic acids research.

[37]  R. Lucito,et al.  Elements required for transcription initiation of the human U2 snRNA gene coincide with elements required for snRNA 3′ end formation. , 1988, The EMBO journal.

[38]  S. Smale,et al.  Mechanism of initiator-mediated transcription: evidence for a functional interaction between the TATA-binding protein and DNA in the absence of a specific recognition sequence. , 1993, Molecular and cellular biology.

[39]  P. Sharp,et al.  Octamer-binding proteins from B or HeLa cells stimulate transcription of the immunoglobulin heavy-chain promoter in vitro. , 1988, Genes & development.

[40]  W. Herr,et al.  The SV40 enhancer contains two distinct levels of organization , 1988, Nature.

[41]  P. Chambon,et al.  Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts , 1986, Nature.

[42]  W. Herr,et al.  Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter , 1992, Cell.

[43]  W. Herr,et al.  The POU domain is a bipartite DNA-binding structure , 1988, Nature.

[44]  D. Reinberg,et al.  Factors involved in specific transcription by mammalian RNA polymerase II. Role of factors IID and MLTF in transcription from the adenovirus major late and IVa2 promoters. , 1989, The Journal of biological chemistry.

[45]  C. Fernandez-Tomas The presence of viral-induced proteins in nuclei from poliovirus-infected HeLa cells. , 1982, Virology.

[46]  W. Herr,et al.  The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. , 1988, Genes & development.