Home LiteratureArticle Details
PMID: 10490602 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins.

Molecular and cellular biology ·Vol. 19 ·No. 10 ·1999-10-00 ·Pages 6632-41

Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE

Abstract

Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters. Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RB "pocket." The mechanism by which these two repression functions occupy the pocket is unknown. A known RB-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RB family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function.

MeSH Terms
Binding Sites Carrier Proteins/genetics,metabolism Gene Expression Regulation Histone Deacetylases/metabolism Models, Genetic Mutation Protein Binding Retinoblastoma Protein/metabolism Sequence Deletion Transcription, Genetic
Chemicals
Carrier Proteins Retinoblastoma Protein Histone Deacetylases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lai A
Departments of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Lee J M
Yang W M
DeCaprio J A
Kaelin W G
Seto E
Branton P E
References (47)
47 references, click to expand
  1. Characterization of the retinoblastoma binding proteins RBP1 and RBP2.
    Oncogene. 1993 Nov;8(11):3149-56 PMID: 8414517
  2. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties.
    Cell. 1992 Jul 24;70(2):351-64 PMID: 1638635
  3. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes.
    Mol Cell Biol. 1993 Dec;13(12):7267-77 PMID: 8246949
  4. Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53.
    Genes Dev. 1994 Jan;8(2):190-202 PMID: 8299938
  5. Functional importance of complex formation between the retinoblastoma tumor suppressor family and adenovirus E1A proteins as determined by mutational analysis of E1A conserved region 2.
    J Virol. 1994 Oct;68(10):6697-709 PMID: 8084002
  6. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest.
    Cell. 1994 Oct 7;79(1):119-30 PMID: 7923370
  7. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter.
    Genes Dev. 1994 Jul 1;8(13):1526-37 PMID: 7958837
  8. The retinoblastoma susceptibility gene product represses transcription when directly bound to the promoter.
    J Biol Chem. 1995 Apr 14;270(15):8837-43 PMID: 7721791
  9. The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4467-71 PMID: 7538672
  10. Direct transcriptional repression by pRB and its reversal by specific cyclins.
    Mol Cell Biol. 1995 Jun;15(6):3256-65 PMID: 7760821
  11. Mechanism of active transcriptional repression by the retinoblastoma protein.
    Nature. 1995 Jun 29;375(6534):812-5 PMID: 7596417
  12. A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.
    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11544-8 PMID: 8524800
  13. Regulation of the cyclin E gene by transcription factor E2F1.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12146-50 PMID: 8618861
  14. Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein.
    Nature. 1992 May 7;357(6373):82-5 PMID: 1533443
  15. Cell cycle regulation of the human cdc2 gene.
    EMBO J. 1992 May;11(5):1797-804 PMID: 1582409
  16. Adenovirus E1A makes two distinct contacts with the retinoblastoma protein.
    J Virol. 1992 Jul;66(7):4606-11 PMID: 1534854
  17. Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene.
    Mol Cell Biol. 1992 Aug;12(8):3431-8 PMID: 1385853
  18. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.
    Science. 1996 Apr 19;272(5260):408-11 PMID: 8602529
  19. Domains A and B in the Rb pocket interact to form a transcriptional repressor motif.
    Mol Cell Biol. 1996 Sep;16(9):4862-8 PMID: 8756645
  20. Histone acetylation and chromatin assembly: a single escort, multiple dances?
    Cell. 1996 Oct 4;87(1):5-8 PMID: 8858142
  21. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12845-50 PMID: 8917507
  22. Dual mechanisms of repression of E2F1 activity by the retinoblastoma gene product.
    EMBO J. 1996 Nov 1;15(21):5917-27 PMID: 8918469
  23. HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family.
    Genes Dev. 1997 Feb 1;11(3):383-96 PMID: 9030690
  24. Regulation of p53-dependent apoptosis, transcriptional repression, and cell transformation by phosphorylation of the 55-kilodalton E1B protein of human adenovirus type 5.
    J Virol. 1997 May;71(5):3620-7 PMID: 9094635
  25. What's up and down with histone deacetylation and transcription?
    Cell. 1997 May 2;89(3):325-8 PMID: 9150131
  26. Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression.
    Cell. 1997 May 2;89(3):349-56 PMID: 9150134
  27. Histone acetylation in chromatin structure and transcription.
    Nature. 1997 Sep 25;389(6649):349-52 PMID: 9311776
  28. RB and hbrm cooperate to repress the activation functions of E2F1.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11268-73 PMID: 9326598
  29. Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family.
    J Biol Chem. 1997 Oct 31;272(44):28001-7 PMID: 9346952
  30. Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells.
    Biochem Biophys Res Commun. 1998 Jan 26;242(3):648-52 PMID: 9464271
  31. Retinoblastoma protein recruits histone deacetylase to repress transcription.
    Nature. 1998 Feb 5;391(6667):597-601 PMID: 9468139
  32. Retinoblastoma protein represses transcription by recruiting a histone deacetylase.
    Nature. 1998 Feb 5;391(6667):601-5 PMID: 9468140
  33. Rb interacts with histone deacetylase to repress transcription.
    Cell. 1998 Feb 20;92(4):463-73 PMID: 9491888
  34. Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7.
    Nature. 1998 Feb 26;391(6670):859-65 PMID: 9495340
  35. Histone acetylation and transcriptional regulatory mechanisms.
    Genes Dev. 1998 Mar 1;12(5):599-606 PMID: 9499396
  36. Characterization of a human RPD3 ortholog, HDAC3.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2795-800 PMID: 9501169
  37. A role for histone deacetylase activity in HDAC1-mediated transcriptional repression.
    Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3519-24 PMID: 9520398
  38. SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex.
    Mol Cell. 1998 Jun;1(7):1021-31 PMID: 9651585
  39. The regulation of E2F by pRB-family proteins.
    Genes Dev. 1998 Aug 1;12(15):2245-62 PMID: 9694791
  40. The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10493-8 PMID: 9724731
  41. The COOH-terminal region of pRb2/p130 binds to histone deacetylase 1 (HDAC1), enhancing transcriptional repression of the E2F-dependent cyclin A promoter.
    Cancer Res. 1998 Nov 15;58(22):5049-52 PMID: 9823308
  42. E2F and histone deacetylase mediate transforming growth factor beta repression of cdc25A during keratinocyte cell cycle arrest.
    Mol Cell Biol. 1999 Jan;19(1):916-22 PMID: 9858615
  43. Mechanism of transcriptional repression of E2F by the retinoblastoma tumor suppressor protein.
    Mol Cell. 1999 Feb;3(2):195-205 PMID: 10078202
  44. RBP1 induces growth arrest by repression of E2F-dependent transcription.
    Oncogene. 1999 Mar 25;18(12):2091-100 PMID: 10321733
  45. Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product.
    Nature. 1991 Jul 18;352(6332):251-4 PMID: 1857421
  46. Retinoblastoma protein switches the E2F site from positive to negative element.
    Nature. 1992 Jul 16;358(6383):259-61 PMID: 1321348
  47. A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
    Cell. 1993 Nov 19;75(4):779-90 PMID: 8242749
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.10.6632
Published
1999-10-00
Pages
6632-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84642
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.10.6632 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