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Results for “Host Cell Factor C1”

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At least 19 recordsLinked to original sources

PubMed1997

The mouse homologue of the human transcription factor C1 (host cell factor). Conservation of forms and function.

The assembly of the herpes simplex virus (HSV) alpha/IE gene enhancer complex is determined by the interactions of the Oct-1 POU domain protein, the viral alphaTIF (alpha-trans-induction factor, VP16, ICP25, VMW65), and the C1 factor (host cell factor, HCF). A unique transcription factor, C1 consists of a family of polypeptides derived from a common precursor by site-specific proteolytic processing. To analyze the role of this factor in the determination of HSV lytic-latent infection, cDNAs and genomic DNAs encoding the mouse homologue have been isolated. This factor is nearly identical to the human protein, contains multiple consensus proteolytic processing sites, and functions efficiently in the assembly of a specific HSV enhancer complex. Interestingly, the differential expression of the C1 factors in both human and mouse tissues may be important for the determination of HSV tissue tropism in these two organisms.

Amino Acid Sequence↗

PubMed1999

Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency.

After a primary infection, herpes simplex virus is maintained in a latent state in neurons of sensory ganglia until complex stimuli reactivate viral lytic replication. Although the mechanisms governing reactivation from the latent state remain unknown, the regulated expression of the viral immediate early genes represents a critical point in this process. These genes are controlled by transcription enhancer complexes whose assembly requires and is coordinated by the cellular C1 factor (host cell factor). In contrast to other tissues, the C1 factor is not detected in the nuclei of sensory neurons. Experimental conditions that induce the reactivation of herpes simplex virus in mouse model systems result in rapid nuclear localization of the protein, indicating that the C1 factor is sequestered in these cells until reactivation signals induce a redistribution of the protein. The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle.

Animals↗

PubMed2000

A novel 50-kilodalton fragment of host cell factor 1 (C1) in G(0) cells.

Host cell factor 1 (HCF-1; also called C1) is a 230-kDa protein which is cleaved posttranslationally into separate but associated N- and C-terminal polypeptides. These polypeptides are components of the C1 complex, along with Oct-1 and the viral protein VP16. The C1 complex is formed when herpes simplex virus (HSV) infects a cell and is responsible for transcription of the HSV immediate-early genes. A temperature-sensitive mutation in the N-terminal kelch domain of HCF-1 reversibly arrests cells in a G(0)-like state when grown at the nonpermissive temperature, and the same domain interacts with VP16 in the formation of the C1 complex. The form of HCF-1 in primary G(0) cells was investigated by using peripheral blood mononucleocytes and serum-arrested human primary fibroblasts. A novel 50-kDa N-terminal fragment of HCF-1 encompassing the kelch domain was identified in the cytoplasm of these cells. This fragment arises by proteolysis of the full-length HCF-1 protein and is able to associate with VP16.

Carrier Proteins↗

PubMed1991

The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain.

The homeo domain of the Oct-1 transcription factor directs formation of a multiprotein-DNA complex containing Oct-1, the herpes simplex virus (HSV) trans-activator VP16, and a second host cell factor (HCF). This VP16-induced complex alters the regulatory activity of Oct-1, in part, by associating it with the potent VP16 acidic transcriptional activation domain. Here, we show that in the absence of HCF, VP16 can recognize specifically the Oct-1 homeo domain. A region of VP16 near the acidic activation domain appears to be involved exclusively in homeo domain recognition because a 4-amino-acid insertion within this region only affects the ability of VP16 to interact with Oct-1, leaving its DNA- and HCF-binding activities unchanged. A 33-amino-acid peptide containing this region complexes with the Oct-1 POU domain bound to DNA, suggesting that this VP16 region contains an autonomous homeo domain recognition subdomain.

Amino Acid Sequence↗

PubMed2002

PDCD2 is a negative regulator of HCF-1 (C1).

Temperature sensitive mutations in host cell factor 1 (HCF-1) arrest cells in the middle of the G1 phase of the cycle. We have shown that the highly conserved C-terminal WYF domain of HCF-1 protein interacts with the MYND domain of the PDCD2 protein. This inter-action is conserved between human HCF-1 and HCF-2 and the C. elegans HCF. Overexpression of PDCD2, which interacts with the N-CoR/mSin3A corepressor complexes, suppresses cotransfected HCF-1 complement-ation of a temperature lesion in the endogenous HCF-1 protein. Overexpression of domains of either PDCD2 or HCF-1, which should interfere with interactions between these two proteins, enhances the complementation.

Amino Acid Sequence↗

PubMed2000

Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16.

Host cell factor (HCF, C1, VCAF or CFF) is a cellular protein that is required for transcription activation of herpes simplex virus (HSV) immediate-early (IE) genes by the virion protein VP16. The biological function of HCF remains unclear. Recently we identified a cellular transcription activator, Luman. As with VP16, the transactivation function of Luman is also regulated by HCF. Here we report a second human protein, Zhangfei (ZF) that interacts with HCF in a fashion similar to Luman and VP16. Although ZF shares no significant sequence homology with Luman, the two proteins have some structural similarities. These include: a basic domain-leucine zipper (bZIP) region, an acidic activation domain and a consensus HCF-binding motif. Unlike Luman, or most other bZIP proteins, ZF by itself did not appear to bind consensus bZIP-binding sites. It was also unable to activate promoters containing these response elements. Although in transient expression assays ectopically expressed ZF was unable to block transactivation by VP16 of a HSV IE promoter, ZF could prevent the expression of several HSV proteins in cells infected with the virus. The ability of ZF to block the synthesis of the HSV IE protein ICP0 relied on its binding to HCF, since a mutant of ZF that was unable to bind HCF was also unable to prevent viral IE protein expression.

5' Untranslated Regions↗

PubMed2000

Association of a protein phosphatase 1 activity with the human factor C1 (HCF) complex.

We have screened a human cDNA expression library with a digoxygenin-labelled protein phosphatase 1 (PP1) probe to identify novel PP1 interacting proteins. Eleven cDNA clones were isolated, which included genes encoding two previously characterised and six novel PP1 binding proteins. Three of the cDNAs encoded a protein called host cell factor (HCF), which is an essential component of the cellular complex required for the transcription of the herpes simplex virus (HSV) immediate-early (IE) genes. We demonstrate that HCF and PP1 exist as a complex in nuclear extracts and that this complex is distinct from the form of HCF that associates with HSV VP16. The data suggest novel roles for HCF and PP1, which may be relevant to their functions in transcription and cell cycle progression.

Apoptosis Regulatory Proteins↗

PubMed2002

A novel function for human factor C1 (HCF-1), a host protein required for herpes simplex virus infection, in pre-mRNA splicing.

Human factor C1 (HCF-1) is needed for the expression of herpes simplex virus 1 (HSV-1) immediate-early genes in infected mammalian cells. Here, we provide evidence that HCF-1 is required for spliceosome assembly and splicing in mammalian nuclear extracts. HCF-1 interacts with complexes containing splicing snRNPs in uninfected mammalian cells and is a stable component of the spliceosome complex. We show that a missense mutation in HCF-1 in the BHK21 hamster cell line tsBN67, at the non-permissive temperature, inhibits the protein's interaction with U1 and U5 splicing snRNPs, causes inefficient spliceosome assembly and inhibits splicing. Transient expression of wild-type HCF-1 in tsBN67 cells restores splicing at the non-permissive temperature. The inhibition of splicing in tsBN67 cells correlates with the temperature-sensitive cell cycle arrest phenotype, suggesting that HCF-1-dependent splicing events may be required for cell cycle progression.

Cell Nucleus↗

PubMed2000

Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): a potential role for proteolytic regulation of coactivator function.

Site-specific proteolysis is an important biological mechanism for the regulation of cellular processes such as gene expression, cell signaling, development, and apoptosis. In transcriptional regulation, specific proteolysis regulates the localization and activity of many regulatory factors. The C1 factor (HCF), a cellular transcription factor and coactivator, undergoes site-specific proteolytic processing at a series of unusual amino acid reiterations to generate a family of amino- and carboxyl-terminal polypeptides that remain tightly associated. Expression and purification of bacterially expressed domains of the C1 factor identifies an autocatalytic activity that is responsible for the specific cleavage of the reiterations. In addition, coexpression of the autocatalytic domain with a heterologous protein containing a target cleavage site demonstrates that the C1 protease may also function in trans.

Amino Acid Sequence↗

PubMed1992

Recognition of the surface of a homeo domain protein.

Homeo domain proteins exhibit distinct biological functions with specificities that cannot be predicted by their sequence specificities for binding DNA. Recognition of the surface of the Oct-1 POU homeo domain provides a general model for the contribution of selective protein-protein interactions to the functional specificity of the homeo domain family of factors. The assembly of Oct-1 into a multiprotein complex on the herpes simplex virus alpha/IE enhancer is specified by the interactions of its homeo domain with ancillary factors. This complex (C1 complex) is composed of the viral alpha TIF protein (VP16), Oct-1, and one additional cellular component, the C1 factor. Variants of the Oct-1 POU homeo domain were generated by site-directed mutagenesis, which altered the residues predicted to form the exposed surface of the domain-DNA complex. Proteins with single amino acid substitutions on the surface of either helix 1 or 2 of the Oct-1 POU homeo domain had decreased abilities to form the C1 complex. The behavior of these mutants in a cooperative DNA-binding assay with alpha TIF suggested that the Oct-1 POU homeo domain is principally recognized by alpha TIF in the C1 complex. The preferential recognition of Oct-1 over the closely related Oct-2 protein is critically influenced by a single residue on the surface of helix 1 because the introduction of this residue into the Oct-2 POU homeo domain significantly enhanced its ability to form a C1 complex.

Amino Acid Sequence↗

PubMed1993

Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by the herpes simplex virus alpha-trans-induction factor (VP16).

The assembly of specific multiprotein complexes on the herpes simplex virus alpha/IE (immediate early) enhancer elements requires the interactions of the Oct-1 POU homeodomain, the viral alpha TIF (alpha-trans-induction factor) (VP16), and at least one additional cellular factor, the C1 factor. The C1 factor interacts directly with alpha TIF, likely forming an intermediate protein complex that recognizes the Oct-1 homeodomain-DNA complex. The biochemical purification of the mammalian C1 factor suggests that it is composed of multiple subunits of related, but heterogeneous, polypeptides. The interaction of a subset of these polypeptides with alpha TIF is stimulated by post-translational modifications of the C1 proteins, suggesting that this factor may be a critical target for the regulation of the herpes simplex virus alpha/IE transcription.

Amino Acid Sequence↗

PubMed1995

The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides.

The alpha/immediate early genes of herpes simplex virus are regulated by the specific assembly of a multiprotein enhancer complex containing the Oct-1 POU domain protein, the viral alpha-transinduction factor alpha TIF, (VP16, ICP25), and the C1 cellular factor. The C1 factor from mammalian cells is a heterogeneous but related set of polypeptides that interact directly with the alpha-transinduction factor to form a heteromeric protein complex. The isolation of cDNAs encoding the polypeptides of the C1 factor suggests that these proteins are proteolytic products of a novel precursor. The sequence of the amino termini of these polypeptide products indicate that the proteins are generated by site-specific cleavages within a reiterated 20-amino acid sequence. Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types.

Amino Acid Sequence↗

PubMed1995

Analysis of homeodomain function by structure-based design of a transcription factor.

The homeodomain is a 60-amino acid module which mediates critical protein-DNA and protein-protein interactions for a large family of regulatory proteins. We have used structure-based design to analyze the ability of the Oct-1 homeodomain to nucleate an enhancer complex. The Oct-1 protein regulates herpes simplex virus (HSV) gene expression by participating in the formation of a multiprotein complex (C1 complex) which regulates alpha (immediate early) genes. We recently described the design of ZFHD1, a chimeric transcription factor containing zinc fingers 1 and 2 of Zif268, a four-residue linker, and the Oct-1 homeodomain. In the presence of alpha-transinduction factor and C1 factor, ZFHD1 efficiently nucleates formation of the C1 complex in vitro and specifically activates gene expression in vivo. The sequence specificity of ZFHD1 recruits C1 complex formation to an enhancer element which is not efficiently recognized by Oct-1. ZFHD1 function depends on the recognition of the Oct-1 homeodomain surface. These results prove that the Oct-1 homeodomain mediates all the protein-protein interactions that are required to efficiently recruit alpha-transinduction factor and C1 factor into a C1 complex. The structure-based design of transcription factors should provide valuable tools for dissecting the interactions of DNA-bound domains in other regulatory circuits.

Amino Acid Sequence↗

PubMed2000

The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP.

Transcription of the herpes simplex virus 1 (HSV-1) immediate early (IE) genes is determined by multiprotein enhancer complexes. The core enhancer assembly requires the interactions of the POU-homeodomain protein Oct-1, the viral transactivator alphaTIF and the cellular factor C1 (HCF). In this context, the C1 factor interacts with each protein to assemble the stable enhancer complex. In addition, the IE enhancer cores contain adjacent binding sites for other cellular transcription factors such as Sp1 and GA-binding protein (GABP). In this study, a direct interaction of the C1 factor with GABP is demonstrated, defining the C1 factor as the critical coordinator of the enhancer complex assembly. In addition, mutations that reduce the GABP transactivation potential also impair the C1-GABP interaction, indicating that the C1 factor functions as a novel coactivator of GABP-mediated transcription. The interaction and coordinated assembly of the enhancer proteins by the C1 factor may be critical for the regulation of the HSV lytic-latent cycle.

Amino Acid Sequence↗

PubMed1990

Interactions of the Oct-1 POU subdomains with specific DNA sequences and with the HSV alpha-trans-activator protein.

Trans-activation by the herpes simplex virus (HSV) protein, alpha TIF (VP16), is dependent on an inducible enhancer sequence that contains a homolog of the octamer element. An ordered series of multiprotein complexes can be assembled on this enhancer, requiring the interactions of Oct-1, alpha TIF, and two additional cellular factors (C1 and C2). Oct-1 binds to the octamer homolog, whereas alpha TIF, also a sequence-specific DNA-binding protein, recognizes sequences within the HSV enhancer core. The partially purified C1 factor interacts directly with alpha TIF in the absence of DNA and is required to form a stabile Oct-1/alpha TIF/C1 factor complex. The POU domain of Oct-1 is a bipartite sequence recognition structure, as both the POU-specific box and the POU homeo box contribute directly to the recognition of the octamer element. Surprisingly, the POU homeo box alone is sufficient to direct the cooperative binding of alpha TIF and to assemble the Oct-1/alpha TIF/C1 factor complex.

Animals↗

PubMed1993

Proteins interacting with an androgen-responsive unit in the C3(1) gene intron.

The expression of the three genes encoding the components C1, C2 and C3 of prostatic binding protein (PBP) is under androgen control and restricted to the rat ventral prostate. The SstI-PvuII fragment of the first intron of the C3(1) gene displays two binding sites for ubiquitous transcription factors and one for a tissue-specific factor in a 80-bp region upstream of its androgen response element (ARE). The octamer transcription factor 1 (OTF-1) binds to the most distal element (site 1) while a member of the nuclear factor I (NF-I) family recognizes site 2. A third unidentified prostate-specific factor, which also occurs in castrated rats, interacts with the proximal element (site 3). In T-47D cells, both the OTF-1 and the NF-I-like factor can modulate the androgen response of the promoter in a reporter gene construct containing the C3(1) intronic fragment.

Androgen-Binding Protein↗

PubMed1995

Amino acid substitutions in the herpes simplex virus transactivator VP16 uncouple direct protein-protein interaction and DNA binding from complex assembly and transactivation.

The herpes simplex virus transactivator VP16 directs the assembly of a multicomponent protein-DNA complex that requires the participation of two cellular factors, the POU homeodomain protein Oct-1, which binds independently to response elements, and VCAF-1 (VP16 complex assembly factor; also called HCF, C1), a factor that binds directly to VP16. A number of distinct properties of VP16 have been implicated in the assembly of the VP16-induced complex (VIC). These include its independent association with VCAF-1 and, under appropriate conditions, its ability to bind to DNA or to DNA-bound Oct-1 in the absence of VCAF-1. In order to probe the requirements of these individual interactions in the functional assembly of VIC, we mutated selected charged amino acids in two subdomains of VP16 previously shown to be important in protein-DNA complex formation. Purified VP16 proteins were analyzed for their ability to direct protein-DNA complex formation and to interact directly with VCAF-1. Several classes of mutants that were differentially compromised in VCAF-1 interaction, direct DNA binding, and/or association with DNA-bound Oct-1 were obtained. Interestingly, all of the derivatives were still capable of generating the VIC complex in vitro and activating transcription in vivo. Our findings indicate that the cooperative assembly of functional VP16-containing complexes can occur by pathways that do not necessarily require the prior interaction of VP16 with VCAF-1 or the ability of VP16 to bind directly to DNA or associate with DNA-bound Oct-1.

Amino Acid Sequence↗

PubMed1997

Correlation of MIB-1 antigen expression with transcription factors Skn-1, Oct-1, AP-2, and HPV type in cervical intraepithelial neoplasia.

Recently, interest in transcription factor coding genes has emerged in many human diseases. Transcription factors, responding both to extracellular and to intracellular signals, exercise an important regulatory control over the proliferation and differentiation of cells. During the development of CIN (cervical intraepithelial neoplasia) lesions, normal regulation of the cell cycle seems to be disturbed. Transcription factors have been shown in vitro to be intimately involved in the expression of HPV (human papillomavirus) early genes, which affect the development of cervical precancer lesions. To test the relevance of in vitro findings in clinical samples, the expression of transcription factors Skn-1, Oct-1, and AP-2 was analysed in 31 normal cervical epithelial samples and in 55 CIN lesions. The results were correlated with the HPV status and cell proliferation activity of the squamous epithelium as measured by MIB-1 antibody. MIB-1 staining is an applicable marker of CIN, correlating strongly with the CIN grade (P < 0.001). The presence of HPV DNA did not accelerate the cell proliferation rate or change significantly the immunoreactivity of Skn-1, Oct-1, or AP-2 antibodies. The staining patterns of these transcription factors were significantly influenced only by the CIN grade. Transcription factors generally showed weaker expression in the dysplastic samples, although the nuclear staining of AP-2 increased markedly (P = 0.046) in the superficial layer of the CIN III samples. These findings suggest that changes in the expression of transcription factors may be important in studying the proliferative activity of CIN lesions.

Antigens, Nuclear↗