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Gene Review

RBL1  -  retinoblastoma-like 1

Homo sapiens

Synonyms: 107 kDa retinoblastoma-associated protein, CP107, PRB1, Retinoblastoma-like protein 1, cp107, ...
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Disease relevance of RBL1


High impact information on RBL1

  • Previously known as the ultimate recipients of cdk regulatory signals, E2F4/5 and p107 act here as transducers of TGFbeta receptor signals upstream of cdk [5].
  • E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression [5].
  • Comparison analysis of the p107 protein sequence reveals a major region of RB homology extending over 564 residues [6].
  • Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein [6].
  • Thus, these two proteins display similarities of structure that may, at least in part, explain their known functional similarities and suggest a generic function for p107 in cell cycle regulation [6].

Chemical compound and disease context of RBL1


Biological context of RBL1


Anatomical context of RBL1

  • Here, we show that pRb2/p130 and Rb1/p105, but not p107, interact with PAI-2 in both the cytoplasm and nucleus of normal primary human corneal and conjunctival epithelial cells [16].
  • We have determined how the phosphorylation of the retinoblastoma family (pRb, p107, and p130) is governed in individual cell cycle phases of Daudi B-cells during cell cycle exit triggered by alpha-interferon (alpha-IFN). alpha-IFN causes dephosphorylation of pRb and loss of p130 phosphorylated Form 3 [17].
  • We found that during in vitro differentiation of human HaCaT keratinocytes, pRb, p107 and p130 are sequentially expressed, in contrast to the co-expression observed during cell cycle progression in the same cells [18].
  • Terminally differentiated cells, such as neurons and skeletal muscle, showed high expression levels for Rb2/p130, whereas p107 was expressed at higher levels in other cell types such as epithelia of the breast and prostate [4].
  • p107 is active in the nucleolus in non-dividing human granulosa lutein cells [19].

Associations of RBL1 with chemical compounds

  • In model p107 spacer region peptides, phosphorylation of S640 by cyclin D1/Cdk4 is strictly dependent upon an intact RXL motif, but phosphorylation of this site in the absence of an RXL motif can be partially restored by replacement of S643 by arginine [20].
  • Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)) [21].
  • The cancer preventive flavonoid silibinin causes hypophosphorylation of Rb/p107 and Rb2/p130 via modulation of cell cycle regulators in human prostate carcinoma DU145 cells [22].
  • Levels of p185HER2 and the extent of its tyrosine phosphorylation were similar in all transfectant clones, as were levels of pRb1 and p107 [23].
  • However, the co-transfection of pRb and p107 induced the expression of early differentiation markers (keratin k10) and triple transfectants pRb+p107+p130 expressed markers representative of later stages of epidermal differentiation (involucrin) [18].

Physical interactions of RBL1

  • HDAC1 interacts with p107 and Rb through an "LXCXE"-like motif, similar to that used by viral transforming proteins to bind and inactivate pocket proteins [24].
  • Further, a role for this amino-terminal region in growth suppression was uncovered by using p107 mutants unable to bind E2F [25].
  • Recent genetic evidence indicates a requirement for cyclin D1/Cdk4 complexes in p107 inactivation [20].
  • In a first series of experiments, we showed that pRb2/p130 and p107 are not evenly distributed within the nucleus and that cell cycle-dependent binding with E2F4 changes also as a function of their subnuclear localization [26].
  • Dual cyclin-binding domains are required for p107 to function as a kinase inhibitor [27].

Enzymatic interactions of RBL1

  • In contrast, only the cyclin A-cdk complexes phosphorylated the Rb-related p107 protein in vitro [28].
  • A conserved site at Ser842 in the related pocket protein p107 is also preferentially phosphorylated by cdk4/D1 [29].

Regulatory relationships of RBL1

  • p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity [25].
  • The p107 tumor suppressor induces stable E2F DNA binding to repress target promoters [30].
  • In this study we examined the functions of B-Myb required to overcome G1 arrest in Saos-2 cells induced by the retinoblastoma-related p107 protein [31].
  • Evidence that Cdk4/6 activity is inhibited by p16(INK4A) in most pRB(-) cells suggests that p107 and p130 may be underphosphorylated and remain associated with E2Fs during G(1)-S progression in cells that lack pRB [32].
  • Experiments utilizing Gal4-RB and Gal4-p107 chimeric constructs demonstrated that either RB or p107 could directly repress TGF-beta induction of p15(INK4B) gene when tethered to p15(INK4B) promoter through Gal4 DNA binding sites [33].

Other interactions of RBL1

  • E2F family members are functionally regulated, in part, by complex formation with one or more members of the nuclear pocket protein family, RB, p107, and p130 [34].
  • Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases [1].
  • Indeed, we find that the viral transforming protein E1A competes with HDAC1 for p107 interaction [24].
  • However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS [35].
  • The growth suppressor activities of the RB and p107 products are believed to be mediated by the reversible binding of a heterogeneous family of cellular proteins to a conserved T/E1A pocket domain that is present within both proteins [36].

Analytical, diagnostic and therapeutic context of RBL1

  • Using genome-wide chromatin immunoprecipitation, we show that there are distinct classes of genes directly regulated by unique combinations of E2F4, p107, and p130, including a group of genes specifically regulated in cycling cells [37].
  • Immunofluorescence studies on skin sections revealed the presence of pRb and p107 in basal and suprabasal cell layers, whilst p130 is restricted to cells already committed to differentiation in the suprabasal compartments [18].
  • Immunocytochemistry shows that these proteins are expressed in almost all GLC but have different sub-cellular distribution: p107 is concentrated in nucleoli, while p130 and E2F-4 show relatively even nuclear and cytoplasmic distributions [19].
  • Site-directed mutagenesis of these E2F sites revealed that although both sites were important for p107 promoter activity, mutation on the proximal, initiation site copy of the E2F site showed a stronger effect [38].
  • Western blot analysis revealed diminution of cyclin D1, Rb, and p107 protein levels after flavopiridol exposure [39].


  1. Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. Xiao, Z.X., Ginsberg, D., Ewen, M., Livingston, D.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1. Dyson, N., Dembski, M., Fattaey, A., Ngwu, C., Ewen, M., Helin, K. J. Virol. (1993) [Pubmed]
  3. Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Faha, B., Ewen, M.E., Tsai, L.H., Livingston, D.M., Harlow, E. Science (1992) [Pubmed]
  4. Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer. Baldi, A., Esposito, V., De Luca, A., Fu, Y., Meoli, I., Giordano, G.G., Caputi, M., Baldi, F., Giordano, A. Clin. Cancer Res. (1997) [Pubmed]
  5. E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Chen, C.R., Kang, Y., Siegel, P.M., Massagué, J. Cell (2002) [Pubmed]
  6. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Ewen, M.E., Xing, Y.G., Lawrence, J.B., Livingston, D.M. Cell (1991) [Pubmed]
  7. Domain 5 of kininogen inhibits proliferation of human colon cancer cell line (HCT-116) by interfering with G1/S in the cell cycle. Bior, A.D., Pixley, R.A., Colman, R.W. J. Thromb. Haemost. (2007) [Pubmed]
  8. Involvement of pRB-related p107 protein in the inhibition of S phase progression in response to genotoxic stress. Kondo, T., Higashi, H., Nishizawa, H., Ishikawa, S., Ashizawa, S., Yamada, M., Makita, Z., Koike, T., Hatakeyama, M. J. Biol. Chem. (2001) [Pubmed]
  9. E2F-independent transcriptional repression by p107, a member of the retinoblastoma family of proteins. Dagnino, L., Zhu, L., Skorecki, K.L., Moses, H.L. Cell Growth Differ. (1995) [Pubmed]
  10. Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action. Kumar, N.S., Richer, J., Owen, G., Litman, E., Horwitz, K.B., Leslie, K.K. Cancer Res. (1998) [Pubmed]
  11. Effects of cyclic AMP on growth and differentiation of rat retinoblastoma-like tumor cells in vitro. Nishida, T., Mukai, N., Solish, S.P., Pomeroy, M. Invest. Ophthalmol. Vis. Sci. (1982) [Pubmed]
  12. E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Moberg, K., Starz, M.A., Lees, J.A. Mol. Cell. Biol. (1996) [Pubmed]
  13. Inhibition of cyclin D1 kinase activity is associated with E2F-mediated inhibition of cyclin D1 promoter activity through E2F and Sp1. Watanabe, G., Albanese, C., Lee, R.J., Reutens, A., Vairo, G., Henglein, B., Pestell, R.G. Mol. Cell. Biol. (1998) [Pubmed]
  14. Requirement for p27(KIP1) in retinoblastoma protein-mediated senescence. Alexander, K., Hinds, P.W. Mol. Cell. Biol. (2001) [Pubmed]
  15. Genotoxic stress induces expression of E2F4, leading to its association with p130 in prostate carcinoma cells. DuPree, E.L., Mazumder, S., Almasan, A. Cancer Res. (2004) [Pubmed]
  16. Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells. Macaluso, M., Montanari, M., Marshall, C.M., Gambone, A.J., Tosi, G.M., Giordano, A., Massaro-Giordano, M. Cell Death Differ. (2006) [Pubmed]
  17. p130, p107, and pRb are differentially regulated in proliferating cells and during cell cycle arrest by alpha-interferon. Thomas, N.S., Pizzey, A.R., Tiwari, S., Williams, C.D., Yang, J. J. Biol. Chem. (1998) [Pubmed]
  18. Differential expression and functionally co-operative roles for the retinoblastoma family of proteins in epidermal differentiation. Paramio, J.M., Laín, S., Segrelles, C., Lane, E.B., Jorcano, J.L. Oncogene (1998) [Pubmed]
  19. p107 is active in the nucleolus in non-dividing human granulosa lutein cells. Green, C., Chatterjee, R., McGarrigle, H.H., Ahmed, F., Thomas, N.S. J. Mol. Endocrinol. (2000) [Pubmed]
  20. Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4. Leng, X., Noble, M., Adams, P.D., Qin, J., Harper, J.W. Mol. Cell. Biol. (2002) [Pubmed]
  21. Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4. Farkas, T., Hansen, K., Holm, K., Lukas, J., Bartek, J. J. Biol. Chem. (2002) [Pubmed]
  22. The cancer preventive flavonoid silibinin causes hypophosphorylation of Rb/p107 and Rb2/p130 via modulation of cell cycle regulators in human prostate carcinoma DU145 cells. Tyagi, A., Agarwal, C., Agarwal, R. Cell Cycle (2002) [Pubmed]
  23. Ectopic expression of pRb2/p130 suppresses the tumorigenicity of the c-erbB-2-overexpressing SKOV3 tumor cell line. Pupa, S.M., Howard, C.M., Invernizzi, A.M., De Vecchi, R., Giani, C., Claudio, P.P., Colnaghi, M.I., Giordano, A., Ménard, S. Oncogene (1999) [Pubmed]
  24. The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase. Ferreira, R., Magnaghi-Jaulin, L., Robin, P., Harel-Bellan, A., Trouche, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  25. p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity. Woo, M.S., Sánchez, I., Dynlacht, B.D. Mol. Cell. Biol. (1997) [Pubmed]
  26. pRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus. Zini, N., Trimarchi, C., Claudio, P.P., Stiegler, P., Marinelli, F., Maltarello, M.C., La Sala, D., De Falco, G., Russo, G., Ammirati, G., Maraldi, N.M., Giordano, A., Cinti, C. J. Cell. Physiol. (2001) [Pubmed]
  27. Dual cyclin-binding domains are required for p107 to function as a kinase inhibitor. Castaño, E., Kleyner, Y., Dynlacht, B.D. Mol. Cell. Biol. (1998) [Pubmed]
  28. A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. Peeper, D.S., Parker, L.L., Ewen, M.E., Toebes, M., Hall, F.L., Xu, M., Zantema, A., van der Eb, A.J., Piwnica-Worms, H. EMBO J. (1993) [Pubmed]
  29. Defining the substrate specificity of cdk4 kinase-cyclin D1 complex. Grafstrom, R.H., Pan, W., Hoess, R.H. Carcinogenesis (1999) [Pubmed]
  30. The p107 tumor suppressor induces stable E2F DNA binding to repress target promoters. O'Connor, R.J., Schaley, J.E., Feeney, G., Hearing, P. Oncogene (2001) [Pubmed]
  31. B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107. Joaquin, M., Bessa, M., Saville, M.K., Watson, R.J. Oncogene (2002) [Pubmed]
  32. Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells. Cheng, L., Rossi, F., Fang, W., Mori, T., Cobrinik, D. J. Biol. Chem. (2000) [Pubmed]
  33. E2F4-RB and E2F4-p107 complexes suppress gene expression by transforming growth factor beta through E2F binding sites. Li, J.M., Hu, P.P., Shen, X., Yu, Y., Wang, X.F. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  34. E2F-4, a new member of the E2F transcription factor family, interacts with p107. Ginsberg, D., Vairo, G., Chittenden, T., Xiao, Z.X., Xu, G., Wydner, K.L., DeCaprio, J.A., Lawrence, J.B., Livingston, D.M. Genes Dev. (1994) [Pubmed]
  35. Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107. Barbie, T.U., Barbie, D.A., MacLaughlin, D.T., Maheswaran, S., Donahoe, P.K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  36. Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein. Kim, Y.W., Otterson, G.A., Kratzke, R.A., Coxon, A.B., Kaye, F.J. Mol. Cell. Biol. (1994) [Pubmed]
  37. Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells. Balciunaite, E., Spektor, A., Lents, N.H., Cam, H., Te Riele, H., Scime, A., Rudnicki, M.A., Young, R., Dynlacht, B.D. Mol. Cell. Biol. (2005) [Pubmed]
  38. Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. Zhu, L., Zhu, L., Xie, E., Chang, L.S. Mol. Cell. Biol. (1995) [Pubmed]
  39. Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells. Schrump, D.S., Matthews, W., Chen, G.A., Mixon, A., Altorki, N.K. Clin. Cancer Res. (1998) [Pubmed]
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