Home LiteratureArticle Details
PMID: 21878458 Published · ppublish English Journal Article Review

Newly identified aspects of tumor suppression by RB.

Disease models & mechanisms ·Vol. 4 ·No. 5 ·2011-09-00 ·Pages 581-5

Viatour P, Sage J

Abstract

The retinoblastoma (RB) tumor suppressor belongs to a cellular pathway that plays a crucial role in restricting the G1-S transition of the cell cycle in response to a large number of extracellular and intracellular cues. Research in the last decade has highlighted the complexity of regulatory networks that ensure proper cell cycle progression, and has also identified multiple cellular functions beyond cell cycle regulation for RB and its two family members, p107 and p130. Here we review some of the recent evidence pointing to a role of RB as a molecular adaptor at the crossroads of multiple pathways, ensuring cellular homeostasis in different contexts. In particular, we discuss the pro- and anti-tumorigenic roles of RB during the early stages of cancer, as well as the importance of the RB pathway in stem cells and cell fate decisions.

MeSH Terms
Animals Humans Neoplasms/metabolism,pathology Retinoblastoma Protein/metabolism Signal Transduction
Chemicals
Retinoblastoma Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Viatour Patrick
Department of Genetics, Stanford University, Stanford, CA 94305, USA. pviatour@stanford.edu
Sage Julien
References (45)
45 references, click to expand
  1. DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.
    Genes Dev. 2011 Apr 15;25(8):801-13 PMID: 21498570
  2. Cells of origin in cancer.
    Nature. 2011 Jan 20;469(7330):314-22 PMID: 21248838
  3. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress.
    Blood. 2008 Feb 15;111(4):1894-902 PMID: 18048646
  4. Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice.
    Cell. 2007 Oct 19;131(2):378-90 PMID: 17956737
  5. E2F-associated chromatin modifiers and cell cycle control.
    Curr Opin Cell Biol. 2007 Dec;19(6):658-62 PMID: 18023996
  6. Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics.
    Genes Dev. 2004 Jun 15;18(12):1413-22 PMID: 15175242
  7. Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma.
    J Cell Biol. 2002 Jan 7;156(1):185-98 PMID: 11777937
  8. Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein.
    Science. 2005 Feb 18;307(5712):1114-8 PMID: 15653467
  9. Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family.
    Cell Stem Cell. 2008 Oct 9;3(4):416-28 PMID: 18940733
  10. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters.
    Nat Genet. 2000 Jul;25(3):338-42 PMID: 10888886
  11. E2F-1 functions in mice to promote apoptosis and suppress proliferation.
    Cell. 1996 May 17;85(4):549-61 PMID: 8653790
  12. A Postnatal Pax7 Progenitor Gives Rise to Pituitary Adenomas.
    Genes Cancer. 2010 Apr 1;1(4):388-402 PMID: 20811506
  13. The N-terminal domain of the Drosophila retinoblastoma protein Rbf1 interacts with ORC and associates with chromatin in an E2F independent manner.
    PLoS One. 2008 Jul 30;3(7):e2831 PMID: 18665226
  14. Tumor suppression by a severely truncated species of retinoblastoma protein.
    Mol Cell Biol. 2002 May;22(9):3103-10 PMID: 11940667
  15. Division and apoptosis of E2f-deficient retinal progenitors.
    Nature. 2009 Dec 17;462(7275):925-9 PMID: 20016601
  16. Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation.
    Mol Cell. 2008 Aug 22;31(4):520-530 PMID: 18722178
  17. Cellular mechanisms of tumour suppression by the retinoblastoma gene.
    Nat Rev Cancer. 2008 Sep;8(9):671-82 PMID: 18650841
  18. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease.
    Genes Dev. 2008 Jun 15;22(12):1662-76 PMID: 18559481
  19. The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression.
    J Clin Invest. 2010 Dec;120(12):4478-92 PMID: 21099110
  20. Proliferation and cell fate establishment during Arabidopsis male gametogenesis depends on the Retinoblastoma protein.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7257-62 PMID: 19359496
  21. Apoptotic caspases regulate induction of iPSCs from human fibroblasts.
    Cell Stem Cell. 2010 Oct 8;7(4):508-20 PMID: 20887956
  22. Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle.
    Cell Stem Cell. 2010 Aug 6;7(2):198-213 PMID: 20682446
  23. RB regulates pancreas development by stabilizing Pdx1.
    EMBO J. 2011 Apr 20;30(8):1563-76 PMID: 21399612
  24. Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis.
    Genes Dev. 2008 Feb 15;22(4):463-75 PMID: 18258751
  25. RB's original CIN?
    Genes Dev. 2010 Jul 1;24(13):1329-33 PMID: 20551167
  26. RB1, development, and cancer.
    Curr Top Dev Biol. 2011;94:129-69 PMID: 21295686
  27. Direct and indirect effects of the pRb tumor suppressor on autophagy.
    Autophagy. 2011 May;7(5):544-6 PMID: 21325879
  28. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment.
    Cell. 2007 Jun 15;129(6):1081-95 PMID: 17574022
  29. Phosphorylation-induced conformational changes in the retinoblastoma protein inhibit E2F transactivation domain binding.
    J Biol Chem. 2010 May 21;285(21):16286-93 PMID: 20223825
  30. E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8.
    Nature. 2008 Sep 25;455(7212):552-6 PMID: 18794899
  31. Keeping an eye on retinoblastoma control of human embryonic stem cells.
    J Cell Biochem. 2009 Dec 1;108(5):1023-30 PMID: 19760644
  32. Tailoring to RB: tumour suppressor status and therapeutic response.
    Nat Rev Cancer. 2008 Sep;8(9):714-24 PMID: 19143056
  33. CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.
    Nature. 2008 Sep 25;455(7212):547-51 PMID: 18794900
  34. A kinase shRNA screen links LATS2 and the pRB tumor suppressor.
    Genes Dev. 2011 Apr 15;25(8):814-30 PMID: 21498571
  35. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence.
    Cancer Cell. 2010 Apr 13;17(4):376-87 PMID: 20385362
  36. Rescue of myogenic defects in Rb-deficient cells by inhibition of autophagy or by hypoxia-induced glycolytic shift.
    J Cell Biol. 2010 Oct 18;191(2):291-301 PMID: 20937698
  37. Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency.
    Am J Pathol. 2010 Nov;177(5):2645-58 PMID: 20864684
  38. Rb regulates fate choice and lineage commitment in vivo.
    Nature. 2010 Aug 26;466(7310):1110-4 PMID: 20686481
  39. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling.
    Cell. 2009 Jun 12;137(6):1018-31 PMID: 19524506
  40. RB has a critical role in mediating the in vivo checkpoint response, mitigating secondary DNA damage and suppressing liver tumorigenesis initiated by aflatoxin B1.
    Oncogene. 2009 Dec 17;28(50):4434-43 PMID: 19838213
  41. Mutations of N-terminal regions render the retinoblastoma protein insufficient for functions in development and tumor suppression.
    Mol Cell Biol. 1997 Dec;17(12):7342-52 PMID: 9372965
  42. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
    Cell. 2003 Jun 13;113(6):703-16 PMID: 12809602
  43. Insights from mouse models into human retinoblastoma.
    Cell Div. 2008 May 19;3:9 PMID: 18489754
  44. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status.
    J Clin Invest. 2010 Sep;120(9):3296-309 PMID: 20679727
  45. Tumor induction and tissue atrophy in mice lacking E2F-1.
    Cell. 1996 May 17;85(4):537-48 PMID: 8653789
Article Info
Journal
Disease models & mechanisms
Abbr.
Dis Model Mech
ISSN
1754-8411
DOI
10.1242/dmm.008060
Email
pviatour@stanford.edu
Published
2011-09-00
Pages
581-5
Language
English
Region
England
NLM ID
101483332
PMCID
PMC3180221
Subset
IM
External Links
PubMed source DOI: 10.1242/dmm.008060 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: product@genelibs.com

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