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Gene Review

Rbl1  -  retinoblastoma-like 1 (p107)

Mus musculus

Synonyms: 107 kDa retinoblastoma-associated protein, AW547426, PRB1, Retinoblastoma-like protein 1, p107, ...
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Disease relevance of Rbl1

  • Although mutating these genes singly had little or no effect, loss of pRb and p107 or p130 together produced chronic hyperplasia and dysplasia of the small intestinal and colonic epithelium [1].
  • Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants [2].
  • Here we show that B-myb overexpression is able to induce DNA synthesis in p107 growth-arrested human osteosarcoma cells (SAOS2). p107 might exert its growth-suppressive activity by regulating B-myb gene transcription [3].
  • Consistent with these results, expression of HPV-16 E7 induces abnormal centrosome duplication in a cell line that lacks functional pRB and in mouse embryo fibroblasts that are deficient for pRB, p107, and p130 [4].
  • Corresponding with this, morphometric data obtained from the perivascular electric injury of the femoral artery confirmed the lack of enhanced ligation and injury response in the absence of p107 [5].

High impact information on Rbl1

  • Reversal of terminal differentiation mediated by p107 in Rb-/- muscle cells [6].
  • Serum-induced cell cycle reentry, on the other hand, correlated with decreased p107 expression [6].
  • Development of the myogenic phenotype in Rb-/- cells correlated with increased expression of p107, which interacted with myogenic transcription factors [6].
  • Thus, although p107 could substitute for Rb as a cofactor for differentiation, it could not maintain the terminally differentiated state in Rb-/- myotubes [6].
  • Binding and suppression of the Myc transcriptional activation domain by p107 [7].

Biological context of Rbl1

  • While inactivation of Rb alone did not alleviate the senescence response of MEFs, pRB/p107-deficient MEFs, after having adapted to in vitro culturing, continued to proliferate at modest rate [8].
  • Our findings support a model in which pRb in conjunction with p107 plays a central role in regulating epidermal homeostasis [9].
  • Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence [10].
  • 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 [1].
  • In contrast to RB1 and p107, expression of p130 was low throughout embryogenesis [11].

Anatomical context of Rbl1


Associations of Rbl1 with chemical compounds

  • By 8 h of HMBA induction and for the remainder of the differentiation process, the free E2F complex is not detected, and only complexes of slower mobility, which contain p107 and cdk2, are found [15].
  • Biochemically, both LY294002 and Deltap85 decreased levels of p107 and cyclins D2, D3 and E and reduced retinoblastoma protein (pRb) phosphorylation [16].
  • Treatment of cells with either concentration of the sense, AS1, AS2, or 20 microM AS3 oligonucleotides had little effect on either Oil Red O lipid accumulation or induction of p107 protein levels [17].
  • Vanadate treatment caused a significant delay in p107 expression in the first 24 h following stimulation [18].
  • A phosphorothioate antisense RNA approach was utilized to determine if inhibition of p107 expression would block or perturb adipocyte differentiation [17].

Physical interactions of Rbl1

  • The addition of bacterially expressed, purified His-C/EBPalpha to the E2F binding reaction resulted in the disruption of E2F complexes containing p107 in nuclear extracts from C/EBPalpha knockout mouse livers [13].
  • Other E1A mutants, all lacking the ability to alter cell morphologic and growth characteristics while binding pRb but variously lacking the trans domain and binding for p107 and/or p300, displayed undetectable neo-reactivations [19].

Regulatory relationships of Rbl1


Other interactions of Rbl1

  • C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice [13].
  • The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions [24].
  • Retinoblastoma and the related pocket protein p107 act as coactivators of NeuroD1 to enhance gene transcription [25].
  • In cycling cells p107 and p130 also interact with heterodimers comprised of Cdk2 and either A or E cyclins [26].
  • A p107-induced cell cycle block can be released by cyclin D1/cdk4 but not by cyclin E/cdk2 [27].

Analytical, diagnostic and therapeutic context of Rbl1


  1. The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium. Haigis, K., Sage, J., Glickman, J., Shafer, S., Jacks, T. J. Biol. Chem. (2006) [Pubmed]
  2. Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Ruiz, S., Segrelles, C., Bravo, A., Santos, M., Perez, P., Leis, H., Jorcano, J.L., Paramio, J.M. Development (2003) [Pubmed]
  3. B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells. Sala, A., Casella, I., Bellon, T., Calabretta, B., Watson, R.J., Peschle, C. J. Biol. Chem. (1996) [Pubmed]
  4. Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. Duensing, S., Münger, K. J. Virol. (2003) [Pubmed]
  5. Vascular ligation response is independent of p107: stressing the role of the related p130. Sindermann, J.R., Köbbert, C., Bauer, F., Skaletz-Rorowski, A., Hohage, H., Plenz, G., Breithardt, G., March, K.L. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  6. Reversal of terminal differentiation mediated by p107 in Rb-/- muscle cells. Schneider, J.W., Gu, W., Zhu, L., Mahdavi, V., Nadal-Ginard, B. Science (1994) [Pubmed]
  7. Binding and suppression of the Myc transcriptional activation domain by p107. Gu, W., Bhatia, K., Magrath, I.T., Dang, C.V., Dalla-Favera, R. Science (1994) [Pubmed]
  8. Ablation of the retinoblastoma gene family deregulates G(1) control causing immortalization and increased cell turnover under growth-restricting conditions. Dannenberg, J.H., van Rossum, A., Schuijff, L., te Riele, H. Genes Dev. (2000) [Pubmed]
  9. Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis. Ruiz, S., Santos, M., Segrelles, C., Leis, H., Jorcano, J.L., Berns, A., Paramio, J.M., Vooijs, M. Development (2004) [Pubmed]
  10. Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence. Marino, S., Hoogervoorst, D., Brandner, S., Berns, A. Development (2003) [Pubmed]
  11. The retinoblastoma gene family is differentially expressed during embryogenesis. Jiang, Z., Zacksenhaus, E., Gallie, B.L., Phillips, R.A. Oncogene (1997) [Pubmed]
  12. FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest. Laplantine, E., Rossi, F., Sahni, M., Basilico, C., Cobrinik, D. J. Cell Biol. (2002) [Pubmed]
  13. C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Timchenko, N.A., Wilde, M., Darlington, G.J. Mol. Cell. Biol. (1999) [Pubmed]
  14. The retinoblastoma-like protein p130 is involved in the determination of reserve cells in differentiating myoblasts. Carnac, G., Fajas, L., L'honoré, A., Sardet, C., Lamb, N.J., Fernandez, A. Curr. Biol. (2000) [Pubmed]
  15. Changes in E2F DNA-binding activity during induced erythroid differentiation. Richon, V.M., Venta-Perez, G. Cell Growth Differ. (1996) [Pubmed]
  16. Phosphoinositide 3-kinases can act independently of p27Kip1 to regulate optimal IL-3-dependent cell cycle progression and proliferation. Fox, B.C., Crew, T.E., Welham, M.J. Cell. Signal. (2005) [Pubmed]
  17. Antisense suppression of p107 inhibits 3T3-L1 adipocyte differentiation. May, J.S., Prince, A.M., Lyle, R.E., McGehee, R.E. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  18. Early expression of p107 is associated with 3T3-L1 adipocyte differentiation. Liu, K., Guan, Y., MacNicol, M.C., MacNicol, A.M., McGehee, R.E. Mol. Cell. Endocrinol. (2002) [Pubmed]
  19. Genetic analysis of adenovirus E1A: induction of genetic instability and altered cell morphologic and growth characteristics are segregatable functions. Drews, R., Kolker, M., Moran, C., Sachar, D., Chan, V., Schnipper, L. Mutat. Res. (1998) [Pubmed]
  20. Compensation by tumor suppressor genes during retinal development in mice and humans. Donovan, S.L., Schweers, B., Martins, R., Johnson, D., Dyer, M.A. BMC Biol. (2006) [Pubmed]
  21. p107 regulates neural precursor cells in the mammalian brain. Vanderluit, J.L., Ferguson, K.L., Nikoletopoulou, V., Parker, M., Ruzhynsky, V., Alexson, T., McNamara, S.M., Park, D.S., Rudnicki, M., Slack, R.S. J. Cell Biol. (2004) [Pubmed]
  22. Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription. Datta, P.K., Raychaudhuri, P., Bagchi, S. Mol. Cell. Biol. (1995) [Pubmed]
  23. Transforming growth factor-beta1 modulates p107 function in myeloid cells: correlation with cell cycle progression. Bang, O.S., Ruscetti, F.W., Lee, M.H., Kim, S.J., Birchenall-Roberts, M.C. J. Biol. Chem. (1996) [Pubmed]
  24. The RB-related gene Rb2/p130 in neuroblastoma differentiation and in B-myb promoter down-regulation. Raschellà, G., Tanno, B., Bonetto, F., Negroni, A., Claudio, P.P., Baldi, A., Amendola, R., Calabretta, B., Giordano, A., Paggi, M.G. Cell Death Differ. (1998) [Pubmed]
  25. Retinoblastoma and the related pocket protein p107 act as coactivators of NeuroD1 to enhance gene transcription. Batsché, E., Moschopoulos, P., Desroches, J., Bilodeau, S., Drouin, J. J. Biol. Chem. (2005) [Pubmed]
  26. Characterization of transcription factor E2F complexes during muscle and neuronal differentiation. Corbeil, H.B., Whyte, P., Branton, P.E. Oncogene (1995) [Pubmed]
  27. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Beijersbergen, R.L., Carlée, L., Kerkhoven, R.M., Bernards, R. Genes Dev. (1995) [Pubmed]
  28. Developmental expression of p107 mRNA and evidence for alternative splicing of the p107 (RBL1) gene product. Kim, K.K., Soonpaa, M.H., Wang, H., Field, L.J. Genomics (1995) [Pubmed]
  29. Molecular cloning, chromosomal mapping, and expression of the mouse p107 gene. Huppi, K., Siwarski, D., Mock, B.A., Dosik, J., Hamel, P.A. Mamm. Genome (1996) [Pubmed]
  30. Alterations in chromatin conformation are accompanied by reorganization of nonchromatin domains that contain U-snRNP protein p28 and nuclear protein p107. Smith, H.C., Spector, D.L., Woodcock, C.L., Ochs, R.L., Bhorjee, J. J. Cell Biol. (1985) [Pubmed]
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