Disease relevance of HCFC1

• The determined transcribed sequence from a human fetal brain library is identical to that of the recently identified accessory protein HCFC1 (host cell factor, also called C1) that activates herpes simplex virus VP16 (alpha TIF) transactivator protein for association with the octamer motif-binding protein Oct-1 (Cell 74: 115, 1993) [1].
• Host cell factor (HCF) was initially discovered as a cellular co-factor required for the activation of herpes simplex virus immediate early gene expression by the virion associated transactivator VP16 [2].
• HCF-1 was also found to be essential for the induction of varicella zoster virus IE gene expression by ORF10, the VZV ortholog of the HSV IE transactivator VP16, and the autostimulatory IE62 protein [3].
• VP16 forms a complex with cellular factors (Oct1 and host cell factor [HCF]) and TAATGARAT elements (found in all HSV-1 IE promoter/enhancer sequences) to mediate stimulation of IE transcription [4].
• Our objective is to explore interactions between Luman and HCF and to determine if they play a role in the biology of herpesviruses [5].

Psychiatry related information on HCFC1

• The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire) [6].
• OBJECTIVE: To describe child- and family-focused cognitive-behavioral therapy (CFF-CBT), a new developmentally sensitive psychosocial intervention for pediatric bipolar disorder (PBD) that is intended for use along with medication [7].
• In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory) [8].
• After 0.2 mg Ro 16-6028 a decrease of attention, numerical memory, psychomotor activity, wakefulness and CFF was observed, while mood improved at later time periods outlasting the sedation [9].
• Implications of the modified scotoma hypothesis are discussed for (1) the neutral-density-filter test to distinguish functional from organic amblyopia, (2) the reduced CFF threshold for amblyopic eyes, (3) expectations of stereopsis for amblyopes, and (4) possible mechanisms for amblyopia [10].

High impact information on HCFC1

• Upon lytic infection of permissive cells, the herpes simplex virus (HSV) transactivator protein VP16 associates with an accessory protein termed host cell factor (HCF) [11].
• Binding to HCF activates VP16 for association with the octamer motif-binding protein Oct-1, to form a multiprotein-DNA complex responsible for activating transcription of the HSV immediate early genes [11].
• When expressed in human cells, this large open reading frame encodes both the 300 kd and smaller HCF polypeptides, indicating that the smaller polypeptides arise by processing of the 300 kd protein [11].
• Although there is no obvious sequence similarity between HCF and other known proteins, HCF contains eight repeats of a new 26 amino acid motif. cDNAs encoding HCF predict a large open reading frame of 2035 codons [11].
• HCF-1 tethers the Sin3 and Set1/Ash2 transcriptional regulatory complexes together even though they are generally associated with opposite transcriptional outcomes: repression and activation of transcription, respectively [12].

Chemical compound and disease context of HCFC1

• The temperature-sensitive phenotype is reversible and results from a single missense mutation--proline to serine at position 134--in HCF, a cellular protein that, together with the viral protein VP16, activates transcription of herpes simplex virus (HSV) immediate-early genes [13].
• The effects of high-carbohydrate, high plant fiber (HCF) diets on glucose and lipid metabolism of 20 lean men receiving insulin therapy for diabetes mellitus were evaluated on a metabolic ward [14].
• Expression and mutational analysis of Autographa californica nucleopolyhedrovirus HCF-1: functional requirements for cysteine residues [15].
• Measurements of the amplitude and latency of the P3b component of the event-related potential (ERP), simple reaction time (SRT) and four psychomotor tests (VAS, DSST, DSp and CFF) were made on 12 male subjects (aged 19-24 years) 1.0-1.5 and 4.0-4.5 h after single oral doses of triprolidine (7.5 mg), terfenadine (60 mg) and placebo [16].
• CFF-depression, vigilance-decrement and disruption of psychomotor performance has been observed during MC-exposure (200 - 800 ppm; 2-4 hours) [17].

Biological context of HCFC1

• Therefore the YY1 binding site in HCFC1 overlaps the site of a second factor, as has been described in several YY1-site-containing promoters [18].
• Whether the interaction between HCF-1 and LZIP is required for cell proliferation remains to be determined [19].
• In this study, we used directed mutations to show that all six blades of the HCF-1 beta-propeller contribute to VP16-induced complex assembly, association with LZIP, and cell cycle progression [19].
• Host cell factor 1 (HCF-1) is a nuclear protein required for progression through G(1) phase of the cell cycle and, via its association with VP16, transcriptional activation of the herpes simplex virus immediate-early genes [19].
• HCF-1 is a cellular protein required by VP16 to activate the herpes simplex virus (HSV) immediate-early genes [20].

Anatomical context of HCFC1

• HCF-1 is a transcriptional cofactor required for activation of herpes simplex virus immediate-early genes by VP16 as well as less clearly defined roles in cell proliferation, cytokinesis, and spliceosome formation [21].
• The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney [22].
• The form of HCF-1 in primary G(0) cells was investigated by using peripheral blood mononucleocytes and serum-arrested human primary fibroblasts [23].
• The requirements for this protein supports the model whereby the regulated transport of HCF-1 from the cytoplasm to the nucleus in sensory neurons may control IE gene expression and reactivation of these viruses from the latent state [3].
• This cytoplasmic association of Luman and HCF could also be demonstrated in neurons in trigeminal ganglia removed from cattle soon after death [5].

Associations of HCFC1 with chemical compounds

• Here we describe a new cellular HCF-1 beta-propeller domain binding protein, termed HPIP, which contains a functional HCF-binding motif and a leucine-rich nuclear export sequence [20].
• PDCD2 is a negative regulator of HCF-1 (C1) [24].
• Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of the HCF repeat that is important to induce cleavage of a heterologous protein [25].
• A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1 [26].
• The third HCF kelch repeat includes a proline residue (P134) that is mutated to serine in hamster tsBN67 cells, resulting in a temperature-sensitive defect in cell proliferation [27].

Physical interactions of HCFC1

• We have shown that the highly conserved C-terminal WYF domain of HCF-1 protein interacts with the MYND domain of the PDCD2 protein [24].
• Here we report a second human protein, Zhangfei (ZF) that interacts with HCF in a fashion similar to Luman and VP16 [28].
• We show here that E2F4 specifically and directly interacts with HCF-1 [29].
• Luman and VP16 appear to have similar mechanisms for binding HCF, as in vitro each competitively inhibited the binding of the other to HCF [30].
• In cells, FHL2 interacts exclusively with the nonprocessed coactivator and costimulates transcription of an HCF-1-dependent target gene [31].

Regulatory relationships of HCFC1

• Importantly, with several of the mutants we observe a poor correlation between the ability to associate with LZIP and promote cell proliferation in the context of the full HCF-1 amino terminus, arguing that the HCF-1 beta-propeller domain must target other cellular transcription factors in order to contribute to G(1) progression [19].
• These data suggest that HPIP regulates HCF-1 activity by modulating its subcellular localization [20].
• Mutations in the HCF-1 kelch domain known to block cell growth abrogated E2F4 binding to the kelch domain in the absence but not in the presence of the juxtaposed basic region [29].
• HCF binds directly to VP16 and this promotes subsequent interaction of the VP16-HCF complex with the POU DNA-binding domain of Oct-1 and selective assembly onto target sites [32].
• The functional interaction of HCF-1 with FHL2 supports a model in which site-specific proteolysis regulates the interaction of HCF-1 with protein partners and thus can modulate the activity of this coactivator [31].

Other interactions of HCFC1

• Furthermore, HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16 into the nucleus [20].
• The complete sequence of the host cell factor 1 (HCFC1) gene and its promoter: a role for YY1 transcription factor in the regulation of its expression [18].
• This inter-action is conserved between human HCF-1 and HCF-2 and the C. elegans HCF [24].
• The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper protein, luman, in its interaction with HCF [33].
• Mutational analysis showed E2F4 independently targets the kelch domain and the basic domain (residues 450-902) of HCF-1, both of which are required for normal cell-cycle progression via separate determinants [29].

Analytical, diagnostic and therapeutic context of HCFC1

• Site-directed mutagenesis of the HCF (1-380) domain revealed residues E102 and K105 to be critical determinants in support of VIC formation [34].
• Western blot analysis confirmed the presence of VCAF (18 kD) in protein lysates extracted from human smooth muscle cells, endothelial cells, macrophages, and osteoblasts [35].
• To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet [36].
• Here we show by fluorescence in situ hybridization and somatic cell hybrid analysis that the gene encoding human HCF, HCFC1, maps to the q28 region of the X chromosome [22].
• Heterogeneity correction factors (HCF) have been measured using a silicon diode detector arising from bounded heterogeneities consisting of lead, steel, titanium, silver, aluminum, and air cylinders near brachytherapy sources of 125I, 137Cs, and 192Ir [37].

References