Rb1

Summary

Gene Symbol: Rb1
Description: RB transcriptional corepressor 1
Alias: Rb-1, pRb, pp105, retinoblastoma-associated protein, retinoblastoma 1
Species: mouse
Products:     Rb1

Top Publications

  1. Srinivasan S, Mayhew C, Schwemberger S, Zagorski W, Knudsen E. RB loss promotes aberrant ploidy by deregulating levels and activity of DNA replication factors. J Biol Chem. 2007;282:23867-77 pubmed
    ..Collectively, these results demonstrate that deregulated S phase control is a key mechanism by which RB-deficient cells acquire elevated ploidy. ..
  2. Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, et al. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat Genet. 2010;42:83-8 pubmed publisher
    Heterozygosity of the retinoblastoma gene Rb1 elicits tumorigenesis in susceptible tissues following spontaneous loss of the remaining functional allele...
  3. Tracy K, Dibling B, Spike B, Knabb J, Schumacker P, Macleod K. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol. 2007;27:6229-42 pubmed
    ..Loss of pRb resulted in derepression of BNip3, a hypoxia-inducible member of the Bcl-2 superfamily of cell death regulators...
  4. Wirt S, Adler A, Gebala V, Weimann J, Schaffer B, Saddic L, et al. G1 arrest and differentiation can occur independently of Rb family function. J Cell Biol. 2010;191:809-25 pubmed publisher
  5. Takahashi C, Contreras B, Iwanaga T, Takegami Y, Bakker A, Bronson R, et al. Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Nat Genet. 2006;38:118-23 pubmed
    ..Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice...
  6. Oshikawa M, Okada K, Nakajima K, Ajioka I. Cortical excitatory neurons become protected from cell division during neurogenesis in an Rb family-dependent manner. Development. 2013;140:2310-20 pubmed publisher
    ..These results suggest that newly born cortical neurons from progenitors become epigenetically protected from DNA damage and cell division in an Rb family-dependent manner. ..
  7. Chen H, Gu X, Liu Y, Wang J, Wirt S, Bottino R, et al. PDGF signalling controls age-dependent proliferation in pancreatic ?-cells. Nature. 2011;478:349-55 pubmed publisher
    ..The discovery of a conserved pathway controlling age-dependent ?-cell proliferation indicates new strategies for ?-cell expansion. ..
  8. Gutierrez G, Kong E, Sabbagh Y, Brown N, Lee J, Demay M, et al. Impaired bone development and increased mesenchymal progenitor cells in calvaria of RB1-/- mice. Proc Natl Acad Sci U S A. 2008;105:18402-7 pubmed publisher
    We have previously shown that the retinoblastoma protein (pRb) can activate expression of Runx2-dependent, bone-specific genes in cultured cells...
  9. Park K, Martelotto L, Peifer M, Sos M, Karnezis A, Mahjoub M, et al. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med. 2011;17:1504-8 pubmed publisher
    ..Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is ..
  10. Berthet C, Klarmann K, Hilton M, Suh H, Keller J, Kiyokawa H, et al. Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation. Dev Cell. 2006;10:563-73 pubmed
    ..Our results demonstrate that Cdk2 and Cdk4 cooperate to phosphorylate Rb in vivo and to couple the G1/S phase transition to mitosis via E2F-dependent regulation of gene expression. ..

Detail Information

Publications89

  1. Srinivasan S, Mayhew C, Schwemberger S, Zagorski W, Knudsen E. RB loss promotes aberrant ploidy by deregulating levels and activity of DNA replication factors. J Biol Chem. 2007;282:23867-77 pubmed
    ..Collectively, these results demonstrate that deregulated S phase control is a key mechanism by which RB-deficient cells acquire elevated ploidy. ..
  2. Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, et al. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat Genet. 2010;42:83-8 pubmed publisher
    Heterozygosity of the retinoblastoma gene Rb1 elicits tumorigenesis in susceptible tissues following spontaneous loss of the remaining functional allele...
  3. Tracy K, Dibling B, Spike B, Knabb J, Schumacker P, Macleod K. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol. 2007;27:6229-42 pubmed
    ..Loss of pRb resulted in derepression of BNip3, a hypoxia-inducible member of the Bcl-2 superfamily of cell death regulators...
  4. Wirt S, Adler A, Gebala V, Weimann J, Schaffer B, Saddic L, et al. G1 arrest and differentiation can occur independently of Rb family function. J Cell Biol. 2010;191:809-25 pubmed publisher
  5. Takahashi C, Contreras B, Iwanaga T, Takegami Y, Bakker A, Bronson R, et al. Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Nat Genet. 2006;38:118-23 pubmed
    ..Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice...
  6. Oshikawa M, Okada K, Nakajima K, Ajioka I. Cortical excitatory neurons become protected from cell division during neurogenesis in an Rb family-dependent manner. Development. 2013;140:2310-20 pubmed publisher
    ..These results suggest that newly born cortical neurons from progenitors become epigenetically protected from DNA damage and cell division in an Rb family-dependent manner. ..
  7. Chen H, Gu X, Liu Y, Wang J, Wirt S, Bottino R, et al. PDGF signalling controls age-dependent proliferation in pancreatic ?-cells. Nature. 2011;478:349-55 pubmed publisher
    ..The discovery of a conserved pathway controlling age-dependent ?-cell proliferation indicates new strategies for ?-cell expansion. ..
  8. Gutierrez G, Kong E, Sabbagh Y, Brown N, Lee J, Demay M, et al. Impaired bone development and increased mesenchymal progenitor cells in calvaria of RB1-/- mice. Proc Natl Acad Sci U S A. 2008;105:18402-7 pubmed publisher
    We have previously shown that the retinoblastoma protein (pRb) can activate expression of Runx2-dependent, bone-specific genes in cultured cells...
  9. Park K, Martelotto L, Peifer M, Sos M, Karnezis A, Mahjoub M, et al. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med. 2011;17:1504-8 pubmed publisher
    ..Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is ..
  10. Berthet C, Klarmann K, Hilton M, Suh H, Keller J, Kiyokawa H, et al. Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation. Dev Cell. 2006;10:563-73 pubmed
    ..Our results demonstrate that Cdk2 and Cdk4 cooperate to phosphorylate Rb in vivo and to couple the G1/S phase transition to mitosis via E2F-dependent regulation of gene expression. ..
  11. Sankaran V, Orkin S, Walkley C. Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis. Genes Dev. 2008;22:463-75 pubmed publisher
    ..Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation...
  12. Laurie N, Mohan A, McEvoy J, Reed D, Zhang J, Schweers B, et al. Changes in retinoblastoma cell adhesion associated with optic nerve invasion. Mol Cell Biol. 2009;29:6268-82 pubmed publisher
    ..Most importantly, our studies are in agreement with genetic studies on human retinoblastomas, suggesting that changes in this pathway are involved in tumor progression. ..
  13. Calo E, Quintero Estades J, Danielian P, Nedelcu S, Berman S, Lees J. Rb regulates fate choice and lineage commitment in vivo. Nature. 2010;466:1110-4 pubmed publisher
    Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma...
  14. Ho V, Schaffer B, Karnezis A, Park K, Sage J. The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras. Oncogene. 2009;28:1393-9 pubmed publisher
  15. Sahin F, Sladek T. E2F-1 has dual roles depending on the cell cycle. Int J Biol Sci. 2010;6:116-28 pubmed
    ..E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation...
  16. McClellan K, Ruzhynsky V, Douda D, Vanderluit J, Ferguson K, Chen D, et al. Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions. Mol Cell Biol. 2007;27:4825-43 pubmed
    ..This study not only outlines overlapping and distinct functions for E2Fs in neurogenesis but also is the first to establish a physiologically relevant role for the Rb/E2F pathway beyond cell cycle regulation in vivo. ..
  17. Lara M, García Escudero R, Ruiz S, Santos M, Moral M, Martinez Cruz A, et al. Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis. Mol Carcinog. 2008;47:209-21 pubmed
    ..differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107...
  18. Bourgo R, Ehmer U, Sage J, Knudsen E. RB deletion disrupts coordination between DNA replication licensing and mitotic entry in vivo. Mol Biol Cell. 2011;22:931-9 pubmed publisher
    ..Combined, these findings demonstrate the critical role of RB in controlling cell-cycle transitions and underscore the importance of intrinsic tissue environments in resultant phenotypes. ..
  19. Blais A, van Oevelen C, Margueron R, Acosta Alvear D, Dynlacht B. Retinoblastoma tumor suppressor protein-dependent methylation of histone H3 lysine 27 is associated with irreversible cell cycle exit. J Cell Biol. 2007;179:1399-412 pubmed publisher
    The retinoblastoma tumor suppressor protein (pRb) is involved in mitotic exit, promoting the arrest of myoblasts, and myogenic differentiation. However, it is unclear how permanent cell cycle exit is maintained in differentiated muscle...
  20. Santos M, Ruiz S, Lara M, Segrelles C, Moral M, Martínez Cruz A, et al. Susceptibility of pRb-deficient epidermis to chemical skin carcinogenesis is dependent on the p107 allele dosage. Mol Carcinog. 2008;47:815-21 pubmed publisher
    Functional inactivation of the pRb-dependent pathway is a general feature of human cancer. However, only a reduced spectrum of tumors displays inactivation of the Rb gene...
  21. Parisi T, Yuan T, Faust A, Caron A, Bronson R, Lees J. Selective requirements for E2f3 in the development and tumorigenicity of Rb-deficient chimeric tissues. Mol Cell Biol. 2007;27:2283-93 pubmed
    The tumor suppressor function of the retinoblastoma protein pRB is largely dependent upon its capacity to inhibit the E2F transcription factors and thereby cell proliferation...
  22. Strachan G, Kopp A, Koike M, Morgan K, Jordan Sciutto K. Chemokine- and neurotrophic factor-induced changes in E2F1 localization and phosphorylation of the retinoblastoma susceptibility gene product (pRb) occur by distinct mechanisms in murine cortical cultures. Exp Neurol. 2005;193:455-68 pubmed
    The retinoblastoma susceptibility gene product (pRb) and E2F1 have been found to exhibit altered localization and increased staining in several neurodegenerative diseases...
  23. Berman S, West J, Danielian P, Caron A, Stone J, Lees J. Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects. Proc Natl Acad Sci U S A. 2009;106:14932-6 pubmed publisher
    The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130...
  24. Spiller C, Wilhelm D, Koopman P. Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice. Biol Reprod. 2010;82:433-43 pubmed publisher
    ..5 days postcoitum (dpc). Retinoblastoma 1 (RB1), a potent cell cycle regulator, was investigated in XY germ cell arrest by studying germ cell ..
  25. Chong J, Tsai S, Sharma N, Opavsky R, Price R, Wu L, et al. E2f3a and E2f3b contribute to the control of cell proliferation and mouse development. Mol Cell Biol. 2009;29:414-24 pubmed publisher
    ..Together, we conclude that the contributions of E2F3a and E2F3b in cell proliferation and development are context dependent. ..
  26. Zhou Z, Flesken Nikitin A, Nikitin A. Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res. 2007;67:5683-90 pubmed
    ..These findings indicate that p53 and Rb are critically important for the regulation of the prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment. ..
  27. Martin A, Odajima J, Hunt S, Dubus P, Ortega S, Malumbres M, et al. Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer Cell. 2005;7:591-8 pubmed
    ..These results indicate that Cdk2 is not an essential target for p27(Kip1) and p21(Cip1) in cell cycle inhibition and tumor suppression...
  28. Siddiqui H, Fox S, Gunawardena R, Knudsen E. Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. J Cell Physiol. 2007;211:131-7 pubmed
    ..Combined, these analyses demonstrate that loss of RB has global effects on chromatin modifications and dynamics. ..
  29. Mantela J, Jiang Z, Ylikoski J, Fritzsch B, Zacksenhaus E, Pirvola U. The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear. Development. 2005;132:2377-88 pubmed
    ..We show here that the retinoblastoma gene Rb and the encoded protein pRb are expressed in differentiating and mature hair cells...
  30. Matoso A, Zhou Z, Hayama R, Flesken Nikitin A, Nikitin A. Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia. Carcinogenesis. 2008;29:620-8 pubmed
    ..Intriguingly, loss of the wild-type retinoblastoma 1 (Rb) gene also leads to MEN-like phenotype in Rb(+/-) mice...
  31. Haigis K, Sage J, Glickman J, Shafer S, Jacks T. The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium. J Biol Chem. 2006;281:638-47 pubmed
    b>pRb, p107, and p130 are related proteins that play a central role in the regulation of cell cycle progression and terminal differentiation in mammalian cells...
  32. Walkley C, Qudsi R, Sankaran V, Perry J, Gostissa M, Roth S, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008;22:1662-76 pubmed publisher
    ..Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of osteosarcoma is ..
  33. Talluri S, Isaac C, Ahmad M, Henley S, Francis S, Martens A, et al. A G1 checkpoint mediated by the retinoblastoma protein that is dispensable in terminal differentiation but essential for senescence. Mol Cell Biol. 2010;30:948-60 pubmed publisher
    ..Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA replication in senescence that is distinct from its role in permanent cell cycle ..
  34. Pajcini K, Corbel S, Sage J, Pomerantz J, Blau H. Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle. Cell Stem Cell. 2010;7:198-213 pubmed publisher
    ..These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration. ..
  35. Gutsch R, Kandemir J, Pietsch D, Cappello C, Meyer J, Simanowski K, et al. CCAAT/enhancer-binding protein beta inhibits proliferation in monocytic cells by affecting the retinoblastoma protein/E2F/cyclin E pathway but is not directly required for macrophage morphology. J Biol Chem. 2011;286:22716-29 pubmed publisher
    ..Inhibition of proliferation by C/EBP? may be important for coordinated monocytic differentiation. ..
  36. Andreu Vieyra C, Chen R, Matzuk M. Effects of granulosa cell-specific deletion of Rb in Inha-alpha null female mice. Endocrinology. 2007;148:3837-49 pubmed
    ..These findings confirm the importance of P27 as a cell cycle regulator in granulosa cells and suggest functional compensation between RB-like proteins in ovarian tumorigenesis. ..
  37. Zhou Z, Flesken Nikitin A, Levine C, Shmidt E, Eng J, Nikitina E, et al. Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb+/- mice. Cancer Res. 2005;65:787-96 pubmed
  38. Spencer C, Pajovic S, Devlin H, Dinh Q, Corson T, Gallie B. Distinct patterns of expression of the RB gene family in mouse and human retina. Gene Expr Patterns. 2005;5:687-94 pubmed
    Although RB1 function is disrupted in the majority of human cancers, an undefined cell of developing human retina is uniquely sensitive to cancer induction when the RB1 tumor suppressor gene is lost...
  39. Dooley A, Winslow M, Chiang D, Banerji S, Stransky N, Dayton T, et al. Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. 2011;25:1470-5 pubmed publisher
    ..Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC...
  40. Mayhew C, Bosco E, Fox S, Okaya T, Tarapore P, Schwemberger S, et al. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 2005;65:4568-77 pubmed
    ..The retinoblastoma tumor suppressor, pRB, plays a central role in proliferative control by inhibiting inappropriate cell cycle entry...
  41. Viatour P, Somervaille T, Venkatasubrahmanyam S, Kogan S, McLaughlin M, Weissman I, et al. Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family. Cell Stem Cell. 2008;3:416-28 pubmed publisher
    ..The presence of a single p107 allele is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system. ..
  42. Rivadeneira D, Mayhew C, Thangavel C, Sotillo E, Reed C, Grana X, et al. Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology. 2010;138:1920-30 pubmed publisher
    ..These data show that CDK4/6 inhibition is a potent mediator of cytostasis and that RB loss can be readily compensated for in the context of both hepatoma cell lines and liver tissue. ..
  43. Chen D, Chen Y, Forrest D, Bremner R. E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3. Cell Death Differ. 2013;20:931-40 pubmed publisher
    ..Our in vivo analysis of cone photoreceptors provides unequivocal proof that E2f-induces apoptosis independent of E2f1, and reveals distinct E2f1- and E2f2-activated death pathways in response to a single tumorigenic insult. ..
  44. Sun H, Chang Y, Schweers B, Dyer M, Zhang X, Hayward S, et al. An E2F binding-deficient Rb1 protein partially rescues developmental defects associated with Rb1 nullizygosity. Mol Cell Biol. 2006;26:1527-37 pubmed
    b>Rb1 is essential for normal embryonic development, as null mice die in midgestation with widespread unscheduled cell proliferation...
  45. Laurie N, Donovan S, Shih C, Zhang J, Mills N, Fuller C, et al. Inactivation of the p53 pathway in retinoblastoma. Nature. 2006;444:61-6 pubmed
    ..Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal ..
  46. Strati K, Lambert P. Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene in head and neck cancer. Cancer Res. 2007;67:11585-93 pubmed
    ..Although our results do not preclude an important role for the E7-pRb interaction, they highlight the importance of pRb-independent functions of E7 in head and neck carcinogenesis.
  47. Berman S, Yuan T, Miller E, Lee E, Caron A, Lees J. The retinoblastoma protein tumor suppressor is important for appropriate osteoblast differentiation and bone development. Mol Cancer Res. 2008;6:1440-51 pubmed publisher
    ..This observation and the documented interaction between the retinoblastoma protein (pRb) and Runx2 suggests that pRb is important in bone development...
  48. Reed C, Mayhew C, McClendon A, Knudsen E. Unique impact of RB loss on hepatic proliferation: tumorigenic stresses uncover distinct pathways of cell cycle control. J Biol Chem. 2010;285:1089-96 pubmed publisher
    ..Combined, these studies demonstrate that RB loss has disparate effects on the response to unique tumorigenic stresses, which is reflective of distinct mechanisms of cell cycle entry. ..
  49. Wikenheiser Brokamp K. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol Life Sci. 2006;63:767-80 pubmed
    ..This review summarizes the phenotypic consequences of Rb family ablation in mice, and discusses how these findings contribute to the increasingly complex picture of Rb family function in development and tumor suppression. ..
  50. Zhou Z, Flesken Nikitin A, Corney D, Wang W, Goodrich D, Roy Burman P, et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 2006;66:7889-98 pubmed
    ..The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis of human prostate cancer. ..
  51. Jiang Z, Deng T, Jones R, Li H, Herschkowitz J, Liu J, et al. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J Clin Invest. 2010;120:3296-309 pubmed publisher
    ..The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost in both luminal-B and triple-negative tumor (TNT; i.e...
  52. Glickstein S, Monaghan J, Koeller H, Jones T, Ross M. Cyclin D2 is critical for intermediate progenitor cell proliferation in the embryonic cortex. J Neurosci. 2009;29:9614-24 pubmed publisher
  53. Gonzalez Vasconcellos I, Anastasov N, Sanli Bonazzi B, Klymenko O, Atkinson M, Rosemann M. Rb1 haploinsufficiency promotes telomere attrition and radiation-induced genomic instability. Cancer Res. 2013;73:4247-55 pubmed publisher
    Germline mutations of the retinoblastoma gene (RB1) predispose to both sporadic and radiation-induced osteosarcoma, tumors characterized by high levels of genomic instability, and activation of alternative lengthening of telomeres...
  54. Moral M, Segrelles C, Lara M, Martínez Cruz A, Lorz C, Santos M, et al. Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel mouse model for head and neck squamous cell carcinoma. Cancer Res. 2009;69:1099-108 pubmed publisher
    ..These data identify activation of Akt and p53 loss as a major mechanism of oral tumorigenesis in vivo and suggest that blocking these signaling pathways could have therapeutic implications for the management of HNSCC. ..
  55. Berman S, Calo E, Landman A, Danielian P, Miller E, West J, et al. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A. 2008;105:11851-6 pubmed publisher
    ..Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo. ..
  56. Markey M, Bergseid J, Bosco E, Stengel K, Xu H, Mayhew C, et al. Loss of the retinoblastoma tumor suppressor: differential action on transcriptional programs related to cell cycle control and immune function. Oncogene. 2007;26:6307-18 pubmed
  57. Choyce A, Yong M, Narayan S, Mattarollo S, Liem A, Lambert P, et al. Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes. PLoS ONE. 2013;8:e57798 pubmed publisher
    ..Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb) led to reduced epithelial hyperplasia and T cell infiltrate...
  58. Viatour P, Ehmer U, Saddic L, Dorrell C, Andersen J, Lin C, et al. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J Exp Med. 2011;208:1963-76 pubmed publisher
    ..this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130...
  59. Balsitis S, Dick F, Lee D, Farrell L, Hyde R, Griep A, et al. Examination of the pRb-dependent and pRb-independent functions of E7 in vivo. J Virol. 2005;79:11392-402 pubmed
    ..Although E7 protein is best known for its ability to inactivate the retinoblastoma tumor suppressor protein, pRb, many other activities for E7 have been proposed in in vitro studies...
  60. Chong J, Wenzel P, Sáenz Robles M, Nair V, Ferrey A, Hagan J, et al. E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells. Nature. 2009;462:930-4 pubmed publisher
    ..This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles. ..
  61. Choi J, Curtis S, Roy D, Flesken Nikitin A, Nikitin A. 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;177:2645-58 pubmed publisher
    ..Taken together, our studies indicate that local Sca-1low dermal mesenchymal stem/progenitor cells are preferential targets for malignant transformation associated with deficiencies in both p53 and Rb. ..
  62. Gonzalo S, García Cao M, Fraga M, Schotta G, Peters A, Cotter S, et al. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol. 2005;7:420-8 pubmed
    ..Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic ..
  63. Shin M, Pitot H, Lambert P. Pocket proteins suppress head and neck cancer. Cancer Res. 2012;72:1280-9 pubmed publisher
    ..E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene...
  64. Nitta R, Jameson S, Kudlow B, Conlan L, Kennedy B. Stabilization of the retinoblastoma protein by A-type nuclear lamins is required for INK4A-mediated cell cycle arrest. Mol Cell Biol. 2006;26:5360-72 pubmed
    ..Previous studies have indicated that A-type lamins interact with the retinoblastoma protein (pRB)...
  65. Burkhart D, Ngai L, Roake C, Viatour P, Thangavel C, Ho V, et al. Regulation of RB transcription in vivo by RB family members. Mol Cell Biol. 2010;30:1729-45 pubmed publisher
    ..These experiments identify novel regulatory feedback mechanisms within the RB pathway in mammalian cells. ..
  66. Dirlam A, Spike B, Macleod K. Deregulated E2f-2 underlies cell cycle and maturation defects in retinoblastoma null erythroblasts. Mol Cell Biol. 2007;27:8713-28 pubmed
    ..Rb null mice, we have identified E2f-2 as being upregulated in end-stage red cells, where we show it is the major pRb-associated E2f and the predominant E2f detected at key target gene promoters...
  67. Wenzel P, Wu L, de Bruin A, Chong J, Chen W, Dureska G, et al. Rb is critical in a mammalian tissue stem cell population. Genes Dev. 2007;21:85-97 pubmed
    ..We conclude that the Rb pathway plays a critical role in the maintenance of a mammalian stem cell population. ..
  68. Schaffer B, Park K, Yiu G, Conklin J, Lin C, Burkhart D, et al. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 2010;70:3877-83 pubmed publisher
    ..These findings indicate that p130 plays a key tumor suppressor role in SCLC. Rb/p53/p130-mutant mice provide a novel preclinical mouse model to identify novel therapeutic targets against SCLC. ..
  69. Martínez Cruz A, Santos M, García Escudero R, Moral M, Segrelles C, Lorz C, et al. Spontaneous tumor formation in Trp53-deficient epidermis mediated by chromosomal instability and inflammation. Anticancer Res. 2009;29:3035-42 pubmed
  70. McEvoy J, Flores Otero J, Zhang J, Nemeth K, Brennan R, Bradley C, et al. Coexpression of normally incompatible developmental pathways in retinoblastoma genesis. Cancer Cell. 2011;20:260-75 pubmed publisher
    ..Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. ..
  71. Dali Youcef N, Mataki C, Coste A, Messaddeq N, Giroud S, Blanc S, et al. Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure. Proc Natl Acad Sci U S A. 2007;104:10703-8 pubmed
    The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation...
  72. MacLellan W, Garcia A, Oh H, Frenkel P, Jordan M, Roos K, et al. Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb. Mol Cell Biol. 2005;25:2486-97 pubmed
    ..Thus, Rb and p130 have overlapping functional roles in vivo to suppress cell cycle activators, including Myc, and maintain quiescence in postnatal cardiac muscle. ..
  73. Martínez Cruz A, Santos M, Lara M, Segrelles C, Ruiz S, Moral M, et al. Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors. Cancer Res. 2008;68:683-92 pubmed publisher
    ..of SCCs, in organ-transplanted patients the E7 and E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved...
  74. Isaac C, Francis S, Martens A, Julian L, Seifried L, Erdmann N, et al. The retinoblastoma protein regulates pericentric heterochromatin. Mol Cell Biol. 2006;26:3659-71 pubmed
    The retinoblastoma protein (pRb) has been proposed to regulate cell cycle progression in part through its ability to interact with enzymes that modify histone tails and create a repressed chromatin structure...
  75. Scime A, Grenier G, Huh M, Gillespie M, Bevilacqua L, Harper M, et al. Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metab. 2005;2:283-95 pubmed
    ..mice contained markedly elevated numbers of adipogenic precursors that displayed downregulated expression of pRb. Consistent with the hypothesis that pRb is required for adult adipocyte differentiation, Cre-mediated deletion of ..
  76. Seoane M, Iglesias P, Gonzalez T, Dominguez F, Fraga M, Aliste C, et al. Retinoblastoma loss modulates DNA damage response favoring tumor progression. PLoS ONE. 2008;3:e3632 pubmed publisher
    ..In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than ..
  77. Hwang C, Matoso A, Corney D, Flesken Nikitin A, Körner S, Wang W, et al. Wild-type p53 controls cell motility and invasion by dual regulation of MET expression. Proc Natl Acad Sci U S A. 2011;108:14240-5 pubmed publisher
    ..These results also show that the extent of advanced cancer traits, such as invasion, may be determined by alterations in individual components of p53/MET regulatory network. ..
  78. Ajioka I, Martins R, Bayazitov I, Donovan S, Johnson D, Frase S, et al. Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice. Cell. 2007;131:378-90 pubmed
    ..We hereby report that differentiated neurons can proliferate and form cancer while maintaining their differentiated state including neurites and synaptic connections. ..
  79. Walkley C, Shea J, Sims N, Purton L, Orkin S. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007;129:1081-95 pubmed
    ..Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs. ..
  80. Ruiz S, Santos M, Lara M, Segrelles C, Ballestin C, Paramio J. Unexpected roles for pRb in mouse skin carcinogenesis. Cancer Res. 2005;65:9678-86 pubmed
    ..The retinoblastoma gene product (pRb) plays a critical role in cell cycle regulation, differentiation, and inhibition of oncogenic transformation...
  81. Lasorella A, Rothschild G, Yokota Y, Russell R, Iavarone A. Id2 mediates tumor initiation, proliferation, and angiogenesis in Rb mutant mice. Mol Cell Biol. 2005;25:3563-74 pubmed
    ..In human neuroblastoma, the N-Myc-driven expression of Id2 is sufficient and necessary for expression of VEGF. These results establish that aberrant Id2 activity directs initiation and progression of embryonal cancer. ..
  82. Zhao H, Bauzon F, Fu H, Lu Z, Cui J, Nakayama K, et al. Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell. 2013;24:645-59 pubmed publisher
    b>pRb and p53 are two major tumor suppressors. Here, we found that p53 activates expression of Pirh2 and KPC1, two of the three ubiquitin ligases for p27...
  83. Lin W, Cao J, Liu J, Beshiri M, Fujiwara Y, Francis J, et al. Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci U S A. 2011;108:13379-86 pubmed publisher
    ..Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by the retinoblastoma protein (pRB)...
  84. Stengel K, Dean J, Seeley S, Mayhew C, Knudsen E. RB status governs differential sensitivity to cytotoxic and molecularly-targeted therapeutic agents. Cell Cycle. 2008;7:1095-103 pubmed
    ..These results indicate that RB status differentially impacts therapeutic response and should be considered when evaluating the efficacy of molecularly targeted therapeutics. ..
  85. Calbo J, Meuwissen R, van Montfort E, van Tellingen O, Berns A. Genotype-phenotype relationships in a mouse model for human small-cell lung cancer. Cold Spring Harb Symp Quant Biol. 2005;70:225-32 pubmed
    ..but also by a specific set of genetic aberrations, including the loss of the tumor suppressor genes p53 and Rb1 and the amplification of any member of the Myc family of oncogenes...
  86. Francis S, Bergsied J, Isaac C, Coschi C, Martens A, Hojilla C, et al. A functional connection between pRB and transforming growth factor beta in growth inhibition and mammary gland development. Mol Cell Biol. 2009;29:4455-66 pubmed publisher
    ..been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-beta cytostatic signaling, pRB is thought to be dispensable for mammary ..
  87. Lu Z, Marcelin G, Bauzon F, Wang H, Fu H, Dun S, et al. pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J. 2013;32:844-57 pubmed publisher
    b>pRb is frequently inactivated in tumours by mutations or phosphorylation. Here, we investigated whether pRb plays a role in obesity...