Home LiteratureArticle Details
PMID: 9889203 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HCF-dependent nuclear import of VP16.

The EMBO journal ·Vol. 18 ·No. 2 ·1999-01-15 ·Pages 480-9

La Boissière S, Hughes T, O'Hare P

Abstract

Transactivation by VP16 requires the formation of a multicomponent complex, the TAATGAAAT recognition factor complex (TRF.C), that contains in addition to VP16, two cellular proteins, Oct-1 and HCF. 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. Here we demonstrate a novel role of HCF in the intracellular compartmentalization of VP16. We show that while VP16 does not contain a consensus nuclear localization signal (NLS) and is largely cytoplasmic, co-expression with HCF resulted in VP16 nuclear accumulation. A candidate NLS within the C-terminus of HCF was identified and insertion of this motif into green fluorescent protein (GFP) promoted nuclear accumulation. Conversely, removal of this signal from HCF (HCFDeltaNLS) resulted in its cytoplasmic accumulation. Co-expression of HCFDeltaNLS with wild-type (wt) VP16, or of wt HCF with VP16 mutants lacking HCF-binding activity failed to promote the nuclear enrichment of VP16. These results indicate that in addition to its role in stabilizing TRF.C, HCF acts as a nuclear import factor for VP16.

MeSH Terms
Amino Acid Sequence Animals Biological Transport, Active COS Cells Cell Compartmentation Cell Nucleus/metabolism Chlorocebus aethiops DNA-Binding Proteins/genetics,metabolism HeLa Cells Herpes Simplex Virus Protein Vmw65/metabolism Host Cell Factor C1 Humans Molecular Sequence Data Mutation Nuclear Localization Signals Octamer Transcription Factor-1 Subcellular Fractions/metabolism Transcription Factors/genetics,metabolism Transfection Vero Cells
Chemicals
DNA-Binding Proteins HCFC1 protein, human Herpes Simplex Virus Protein Vmw65 Host Cell Factor C1 Nuclear Localization Signals Octamer Transcription Factor-1 POU2F1 protein, human Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
La Boissière S
Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK.
Hughes T
O'Hare P
References (47)
47 references, click to expand
  1. Recognition of the surface of a homeo domain protein.
    Genes Dev. 1992 Nov;6(11):2047-57 PMID: 1358755
  2. A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain.
    Genes Dev. 1992 Nov;6(11):2058-65 PMID: 1358756
  3. The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain.
    Genes Dev. 1991 Dec;5(12B):2555-66 PMID: 1684335
  4. A cellular factor binds to the herpes simplex virus type 1 transactivator Vmw65 and is required for Vmw65-dependent protein-DNA complex assembly with Oct-1.
    Mol Cell Biol. 1990 Sep;10(9):4974-7 PMID: 2167442
  5. Characterization of a cellular factor which interacts functionally with Oct-1 in the assembly of a multicomponent transcription complex.
    Nucleic Acids Res. 1990 Dec 11;18(23):6871-80 PMID: 2175881
  6. Structural requirements in the herpes simplex virus type 1 transactivator Vmw65 for interaction with the cellular octamer-binding protein and target TAATGARAT sequences.
    J Virol. 1990 Jun;64(6):2716-24 PMID: 2335815
  7. Mutational analysis of the herpes simplex virus trans-inducing factor Vmw65.
    Gene. 1989 Feb 20;75(2):213-24 PMID: 2541050
  8. Overlapping octamer and TAATGARAT motifs in the VF65-response elements in herpes simplex virus immediate-early promoters represent independent binding sites for cellular nuclear factor III.
    J Virol. 1989 Jun;63(6):2798-812 PMID: 2542590
  9. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16.
    Nature. 1989 Oct 19;341(6243):624-30 PMID: 2571937
  10. A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence.
    Cell. 1988 Feb 12;52(3):425-34 PMID: 2830986
  11. Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation.
    Cell. 1988 Feb 12;52(3):435-45 PMID: 2830987
  12. A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins.
    Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347-51 PMID: 2842768
  13. Mutational analysis of the herpes simplex virus type 1 trans-inducing factor Vmw65.
    J Gen Virol. 1988 Oct;69 ( Pt 10):2595-605 PMID: 2844968
  14. Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression.
    EMBO J. 1988 Dec 20;7(13):4231-8 PMID: 2854058
  15. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain.
    Genes Dev. 1988 Dec;2(12A):1582-99 PMID: 2905684
  16. Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 alpha genes.
    Proc Natl Acad Sci U S A. 1987 Jan;84(1):71-5 PMID: 3025864
  17. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products.
    Genes Dev. 1988 Dec;2(12A):1513-6 PMID: 3215510
  18. VP16 interacts via its activation domain with VP22, a tegument protein of herpes simplex virus, and is relocated to a novel macromolecular assembly in coexpressing cells.
    J Virol. 1995 Dec;69(12):7932-41 PMID: 7494306
  19. The HCF repeat is an unusual proteolytic cleavage signal.
    Genes Dev. 1995 Oct 15;9(20):2445-58 PMID: 7590226
  20. The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney.
    Genomics. 1995 Jan 20;25(2):462-8 PMID: 7789979
  21. Genomic organization of the human VP16 accessory protein, a housekeeping gene (HCFC1) mapping to Xq28.
    Genomics. 1994 Sep 1;23(1):30-5 PMID: 7829097
  22. The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides.
    J Biol Chem. 1995 Mar 3;270(9):4387-94 PMID: 7876203
  23. Combinatorial control of transcription: the herpes simplex virus VP16-induced complex.
    Cold Spring Harb Symp Quant Biol. 1993;58:167-78 PMID: 7956027
  24. Evaluation of colocalization interactions between the IE110, IE175, and IE63 transactivator proteins of herpes simplex virus within subcellular punctate structures.
    J Virol. 1995 Jan;69(1):476-91 PMID: 7983744
  25. Site-specific conformational alteration of the Oct-1 POU domain-DNA complex as the basis for differential recognition by Vmw65 (VP16).
    Cell. 1994 Dec 2;79(5):841-52 PMID: 8001121
  26. Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.
    J Gen Virol. 1994 May;75 ( Pt 5):1091-9 PMID: 8176370
  27. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein.
    Cell. 1993 Jul 16;74(1):115-25 PMID: 8392914
  28. kelch encodes a component of intercellular bridges in Drosophila egg chambers.
    Cell. 1993 Mar 12;72(5):681-93 PMID: 8453663
  29. 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).
    J Biol Chem. 1993 Mar 25;268(9):6525-34 PMID: 8454622
  30. POU domain transcription factors.
    Biochim Biophys Acta. 1993 Apr 29;1173(1):1-21 PMID: 8485147
  31. Overexpression of the herpes simplex virus type 1 immediate-early regulatory protein, ICP27, is responsible for the aberrant localization of ICP0 and mutant forms of ICP4 in ICP4 mutant virus-infected cells.
    J Virol. 1996 Aug;70(8):5346-56 PMID: 8764045
  32. Multiple interactions control the intracellular localization of the herpes simplex virus type 1 capsid proteins.
    J Gen Virol. 1996 Sep;77 ( Pt 9):2251-60 PMID: 8811025
  33. The chromosome localization and the HCF repeats of the human host cell factor gene (HCFC1) are conserved in the mouse homologue.
    Genomics. 1996 Mar 1;32(2):277-80 PMID: 8833156
  34. Rel/NF-kappaB/IkappaB proteins and cancer.
    Oncogene. 1996 Oct 3;13(7):1367-78 PMID: 8875974
  35. Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
    Genes Dev. 1996 Oct 15;10(20):2527-39 PMID: 8895655
  36. A novel type of protein kinase phosphorylates actin in the actin-fragmin complex.
    EMBO J. 1996 Oct 15;15(20):5547-56 PMID: 8896448
  37. A single-point mutation in HCF causes temperature-sensitive cell-cycle arrest and disrupts VP16 function.
    Genes Dev. 1997 Mar 15;11(6):726-37 PMID: 9087427
  38. Protein interactions in the herpes simplex virus type 1 VP16-induced complex: VP16 peptide inhibition and mutational analysis of host cell factor requirements.
    J Virol. 1997 May;71(5):3886-94 PMID: 9094665
  39. ENC-1: a novel mammalian kelch-related gene specifically expressed in the nervous system encodes an actin-binding protein.
    J Neurosci. 1997 May 1;17(9):3038-51 PMID: 9096139
  40. Nucleocytoplasmic transport: signals, mechanisms and regulation.
    Nature. 1997 Apr 24;386(6627):779-87 PMID: 9126736
  41. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.
    Cell. 1997 May 2;89(3):331-40 PMID: 9150132
  42. Interdigitated residues within a small region of VP16 interact with Oct-1, HCF, and DNA.
    Mol Cell Biol. 1997 Jul;17(7):3937-46 PMID: 9199328
  43. Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor.
    Mol Cell Biol. 1997 Sep;17(9):5117-26 PMID: 9271389
  44. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression.
    Mol Cell Biol. 1997 Oct;17(10):6139-46 PMID: 9315674
  45. Concerted activity of host cell factor subregions in promoting stable VP16 complex assembly and preventing interference by the acidic activation domain.
    Mol Cell Biol. 1997 Dec;17(12):7108-18 PMID: 9372942
  46. Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP.
    Genes Dev. 1997 Dec 1;11(23):3122-7 PMID: 9389645
  47. Nuclear access and action of notch in vivo.
    Cell. 1998 May 15;93(4):649-60 PMID: 9604939
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.2.480
Published
1999-01-15
Pages
480-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171141
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.2.480 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2