Home LiteratureArticle Details
PMID: 19815555 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1.

The Journal of biological chemistry ·Vol. 284 ·No. 49 ·2009-12-04 ·Pages 34179-88

Machida YJ, Machida Y, Vashisht AA, Wohlschlegel JA, Dutta A

Abstract

The deubiquitinating enzyme BRCA1-associated protein 1 (BAP1) possesses growth inhibitory activity and functions as a tumor suppressor. In this study we report that BAP1 also plays positive roles in cell proliferation. BAP1 depletion by RNAi inhibits cell proliferation as does overexpression of a dominant negative mutant of BAP1. Mass spectrometry analyses of copurified proteins revealed that BAP1 is associated with factors involved in chromatin modulation and transcriptional regulation. We show that the interaction with host cell factor-1 (HCF-1), a cell-cycle regulator composed of HCF-1N and HCF-1C, is critical for the BAP1-mediated growth regulation. We found that HCF-1N is modified with Lys-48-linked polyubiquitin chains on its Kelch domain. The HCF-1 binding motif of BAP1 is required for interaction with HCF-1N and mediates deubiquitination of HCF-1N by BAP1. The importance of the BAP1-HCF-1 interaction is underscored by the fact that growth suppression by the dominant negative BAP1 mutant is entirely dependent on the HCF-1 binding motif. These results suggest that BAP1 regulates cell proliferation by deubiquitinating HCF-1.

MeSH Terms
Cell Cycle Cell Line, Tumor Cell Proliferation Chromatin/chemistry Gene Expression Regulation Host Cell Factor C1/metabolism Humans Mass Spectrometry/methods Mutation Protein Binding Protein Processing, Post-Translational Protein Structure, Tertiary Transcription, Genetic Tumor Suppressor Proteins/metabolism Ubiquitin/chemistry Ubiquitin Thiolesterase/metabolism
Chemicals
BAP1 protein, human Chromatin HCFC1 protein, human Host Cell Factor C1 Tumor Suppressor Proteins Ubiquitin Ubiquitin Thiolesterase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Machida Yuichi J
Division of Oncology Research, Mayo College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Machida Yuka
Vashisht Ajay A
Wohlschlegel James A
Dutta Anindya
References (52)
52 references, click to expand
  1. BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity.
    Cancer Res. 2009 Jan 1;69(1):111-9 PMID: 19117993
  2. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression.
    Oncogene. 1998 Mar 5;16(9):1097-112 PMID: 9528852
  3. 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
  4. Targeted comparative RNA interference analysis reveals differential requirement of genes essential for cell proliferation.
    Mol Biol Cell. 2006 Nov;17(11):4837-45 PMID: 16957053
  5. Genome-scale RNAi profiling of cell division in human tissue culture cells.
    Nat Cell Biol. 2007 Dec;9(12):1401-12 PMID: 17994010
  6. PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks.
    Mutat Res. 2008 Dec 1;647(1-2):3-12 PMID: 18682256
  7. DTASelect and Contrast: tools for assembling and comparing protein identifications from shotgun proteomics.
    J Proteome Res. 2002 Jan-Feb;1(1):21-6 PMID: 12643522
  8. Chromatin recruitment of DNA repair proteins: lessons from the fanconi anemia and double-strand break repair pathways.
    Mol Cell. 2008 Nov 7;32(3):306-12 PMID: 18995829
  9. Identification of SUMO-conjugated proteins and their SUMO attachment sites using proteomic mass spectrometry.
    Methods Mol Biol. 2009;497:33-49 PMID: 19107409
  10. Endocytosis: the DUB version.
    Trends Cell Biol. 2006 Nov;16(11):551-9 PMID: 16996268
  11. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression.
    Mol Cell Biol. 1997 Oct;17(10):6139-46 PMID: 9315674
  12. Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1.
    Mol Cell Biol. 2009 Apr;29(8):2181-92 PMID: 19188440
  13. The role of ubiquitin in NF-kappaB regulatory pathways.
    Annu Rev Biochem. 2009;78:769-96 PMID: 19489733
  14. 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
  15. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry.
    Nat Methods. 2007 Mar;4(3):207-14 PMID: 17327847
  16. 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
  17. The kelch repeat superfamily of proteins: propellers of cell function.
    Trends Cell Biol. 2000 Jan;10(1):17-24 PMID: 10603472
  18. Reverse the curse--the role of deubiquitination in cell cycle control.
    Curr Opin Cell Biol. 2008 Apr;20(2):156-63 PMID: 18346885
  19. Linkage of the ubiquitin-conjugating system and the endocytic pathway in ligand-induced internalization of the growth hormone receptor.
    EMBO J. 1997 Aug 15;16(16):4851-8 PMID: 9305627
  20. Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation.
    J Neurosci. 2005 Feb 23;25(8):2002-9 PMID: 15728840
  21. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
    J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89 PMID: 24226387
  22. Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells.
    Mol Cell Biol. 2001 Jun;21(11):3820-9 PMID: 11340173
  23. An automated multidimensional protein identification technology for shotgun proteomics.
    Anal Chem. 2001 Dec 1;73(23):5683-90 PMID: 11774908
  24. Defining the human deubiquitinating enzyme interaction landscape.
    Cell. 2009 Jul 23;138(2):389-403 PMID: 19615732
  25. 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
  26. A novel mammalian flavin-dependent histone demethylase.
    J Biol Chem. 2009 Jun 26;284(26):17775-82 PMID: 19407342
  27. Cancer proliferation gene discovery through functional genomics.
    Science. 2008 Feb 1;319(5863):620-4 PMID: 18239126
  28. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression.
    Mol Cell Biol. 2004 Jul;24(13):5639-49 PMID: 15199122
  29. N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10757-62 PMID: 10984507
  30. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells.
    Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13212-7 PMID: 16141338
  31. DUBs and cancer: the role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors.
    Cell Cycle. 2009 Jun 1;8(11):1688-97 PMID: 19448430
  32. The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection.
    Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10835-40 PMID: 17578910
  33. Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1.
    EMBO J. 2003 May 15;22(10):2360-9 PMID: 12743030
  34. A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16.
    Mol Cell Biol. 2005 Nov;25(21):9175-88 PMID: 16227571
  35. Large-scale analysis of the yeast proteome by multidimensional protein identification technology.
    Nat Biotechnol. 2001 Mar;19(3):242-7 PMID: 11231557
  36. HCF-1 functions as a coactivator for the zinc finger protein Krox20.
    J Biol Chem. 2003 Dec 19;278(51):51116-24 PMID: 14532282
  37. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1.
    Genes Dev. 2003 Apr 1;17(7):896-911 PMID: 12670868
  38. A genomic and functional inventory of deubiquitinating enzymes.
    Cell. 2005 Dec 2;123(5):773-86 PMID: 16325574
  39. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases.
    Mol Cell. 2007 Jul 6;27(1):107-19 PMID: 17612494
  40. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization.
    Cancer Res. 2008 Sep 1;68(17):6953-62 PMID: 18757409
  41. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains.
    EMBO J. 2002 Dec 16;21(24):6755-62 PMID: 12485996
  42. An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13403-8 PMID: 12271126
  43. Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
    Mol Cell Biol. 2000 Nov;20(22):8602-12 PMID: 11046155
  44. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.
    Cell. 2005 Jun 17;121(6):873-85 PMID: 15960975
  45. 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
  46. The HCF repeat is an unusual proteolytic cleavage signal.
    Genes Dev. 1995 Oct 15;9(20):2445-58 PMID: 7590226
  47. Transcriptional regulation by histone ubiquitination and deubiquitination.
    Genes Dev. 2003 Nov 15;17(22):2733-40 PMID: 14630937
  48. Proteasome-independent functions of ubiquitin in endocytosis and signaling.
    Science. 2007 Jan 12;315(5809):201-5 PMID: 17218518
  49. The genomic landscapes of human breast and colorectal cancers.
    Science. 2007 Nov 16;318(5853):1108-13 PMID: 17932254
  50. Iodoacetamide-induced artifact mimics ubiquitination in mass spectrometry.
    Nat Methods. 2008 Jun;5(6):459-60 PMID: 18511913
  51. Homozygous deletion, rearrangement and hypermethylation implicate chromosome region 3p14.3-3p21.3 in sporadic breast-cancer development.
    Int J Cancer. 1994 May 15;57(4):473-9 PMID: 8181852
  52. Analyzing chromatin remodeling complexes using shotgun proteomics and normalized spectral abundance factors.
    Methods. 2006 Dec;40(4):303-11 PMID: 17101441
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M109.046755
Published
2009-12-04
Epub
2009-00-08
Pages
34179-88
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2797188
Subset
IM
Grants
NCI NIH HHS · R01 CA060499 · United States
NCI NIH HHS · R01 CA060499-16 · United States
NCI NIH HHS · R01 CA60499 · United States
External Links
PubMed source DOI: 10.1074/jbc.M109.046755 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