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Gene Review

RBL2  -  retinoblastoma-like 2

Homo sapiens

Synonyms: 130 kDa retinoblastoma-associated protein, P130, RB2, RBR-2, Rb2, ...
 
 
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Disease relevance of RBL2

  • Finally, we subjected 11 lung cancer cell lines to nucleotide sequencing and did not detect mutations within the C-terminal RBL2 exons 19-22 as recently reported [1].
  • Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130 [2].
  • We took advantage of a tetracycline-regulated gene expression system to control the expression of RB2/p130 in JC virus-induced hamster brain tumor cells to study in vivo the molecular mechanisms used by pRb2/p130 to elicit its growth-suppressive function [3].
  • Genetic alterations of the retinoblastoma-related gene RB2/p130 identify different pathogenetic mechanisms in and among Burkitt's lymphoma subtypes [4].
  • We tested the expression and genomic organization of the RB2/p130 gene in relation to the proliferative features of a series of BL samples collected from the endemic and sporadic regions, regardless of whether the samples were acquired immune deficiency syndrome (AIDS)-related [4].
 

Psychiatry related information on RBL2

  • INTERPRETATION: 2-DE for p130/131 is a specific test for the diagnosis of CJD [5].
 

High impact information on RBL2

  • The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins [6].
  • In vitro, recombinant Skp2 was able to bind hyperphosphorylated but not dephosphorylated p130 [7].
  • Our results indicate that the decline of p130 expression as G0 cells reenter the cell cycle is due to a decrease in protein stability [7].
  • Furthermore, in vitro polyubiquitination of p130 by SCF(Skp2) was specifically dependent on phosphorylation of p130 on Serine 672 [7].
  • The mechanism of down-regulation of p130 expression in proliferating cells was investigated [7].
 

Chemical compound and disease context of RBL2

 

Biological context of RBL2

 

Anatomical context of RBL2

 

Associations of RBL2 with chemical compounds

  • 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].
  • The assays also showed that the specific binding of E2F4/p130 complex to the distal site was dramatically impaired by a mutation introduced into the contiguous repression site (cell Cycle gene Homology Region; CHR) [23].
  • Furthermore, the destabilization of p130 correlated with a decrease in the expression of involucrin, a differentiation marker [24].
  • Engagement of beta1 integrins in terminally differentiated human B cell lines, such as ARH-77, leads to prominent tyrosine phosphorylation of the p130 Crk-associated substrate (Cas) [25].
 

Physical interactions of RBL2

  • By using a specific E2F-5 antiserum, we found that under physiological conditions, E2F-5 interacts preferentially with p130 [15].
  • Interestingly, pRb2/p130 expression negatively modulated the binding of p27Kip1 to JCV TAg [3].
  • These studies suggest that TGF-beta1 may enhance HDAC1 binding to p130 in vivo, thereby inhibiting cdc25A gene expression [26].
  • Induction of E7 function was not correlated with binding to p130 or pRb but rather with intranuclear localization and modest induction of binding to p107 [27].
  • In this study, we show that the signaling molecule Raf-1 can physically interact with Rb and p130 proteins in vitro and in vivo and that this interaction can be detected in mammalian cells without overexpressing any component [28].
 

Enzymatic interactions of RBL2

  • Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence [14].
  • These findings show that p130 can be phosphorylated and functionally inactivated in a Cdk2-dependent process, and they highlight the involvement of distinct Cdks in the regulation of different pRB family proteins [29].
 

Co-localisations of RBL2

  • Following radiation treatment, E2F4 colocalized with p130 in the nucleus during a radiation-induced stable G(2)-phase arrest [30].
 

Regulatory relationships of RBL2

 

Other interactions of RBL2

  • Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to interact with p130 in a yeast two-hybrid system [2].
  • Its activity is controlled by the cell cycle regulators pRB, p107, and p130 [34].
  • E2F-5, a new E2F family member that interacts with p130 in vivo [15].
  • The growth inhibitory activity of pRb2/p130 also correlated with its E2F-binding capacity [3].
  • Furthermore, p27Kip1 and pRb2/p130 were found to be targets of the JCV TAg oncoprotein and to interact in vivo with each other independently from the presence of TAg [3].
 

Analytical, diagnostic and therapeutic context of RBL2

  • The structures of exons 19 through 22 of the RB2/p130 gene, encoding for the B domain and C terminus, were analyzed by polymerase chain reaction (PCR) analysis and single-strand conformation polymorphism (SSCP) technique [4].
  • Using oligonucleotide arrays, a number of Rb2/p130 downregulated genes were identified and their regulation was confirmed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis [35].
  • In conclusion, coupling adenoviral overexpression with microarray and semiquantitative RT-PCR analyses proved to be a versatile strategy for identifying pRb2/p130 target genes and for better understanding the expression profiles of these genes [35].
  • pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis [35].
  • METHODS: Northern blot hybridization analyses were performed on samples of total cellular RNA to measure RB2/p130 and beta-actin messenger RNA levels [36].

References

  1. Protein expression of the RB-related gene family and SV40 large T antigen in mesothelioma and lung cancer. Modi, S., Kubo, A., Oie, H., Coxon, A.B., Rehmatulla, A., Kaye, F.J. Oncogene (2000) [Pubmed]
  2. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Sardet, C., Vidal, M., Cobrinik, D., Geng, Y., Onufryk, C., Chen, A., Weinberg, R.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Inducible pRb2/p130 expression and growth-suppressive mechanisms: evidence of a pRb2/p130, p27Kip1, and cyclin E negative feedback regulatory loop. Howard, C.M., Claudio, P.P., De Luca, A., Stiegler, P., Jori, F.P., Safdar, N.M., Caputi, M., Khalili, K., Giordano, A. Cancer Res. (2000) [Pubmed]
  4. Genetic alterations of the retinoblastoma-related gene RB2/p130 identify different pathogenetic mechanisms in and among Burkitt's lymphoma subtypes. Cinti, C., Leoncini, L., Nyongo, A., Ferrari, F., Lazzi, S., Bellan, C., Vatti, R., Zamparelli, A., Cevenini, G., Tosi, G.M., Claudio, P.P., Maraldi, N.M., Tosi, P., Giordano, A. Am. J. Pathol. (2000) [Pubmed]
  5. Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid. Zerr, I., Bodemer, M., Otto, M., Poser, S., Windl, O., Kretzschmar, H.A., Gefeller, O., Weber, T. Lancet (1996) [Pubmed]
  6. The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. De Luca, A., Baldi, A., Esposito, V., Howard, C.M., Bagella, L., Rizzo, P., Caputi, M., Pass, H.I., Giordano, G.G., Baldi, F., Carbone, M., Giordano, A. Nat. Med. (1997) [Pubmed]
  7. The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2). Tedesco, D., Lukas, J., Reed, S.I. Genes Dev. (2002) [Pubmed]
  8. Protein phosphatase 2A associates with Rb2/p130 and mediates retinoic acid-induced growth suppression of ovarian carcinoma cells. Vuocolo, S., Purev, E., Zhang, D., Bartek, J., Hansen, K., Soprano, D.R., Soprano, K.J. J. Biol. Chem. (2003) [Pubmed]
  9. pRb2/p130 decreases sensitivity to apoptosis induced by camptothecin and doxorubicin but not by taxol. Tonini, T., Gabellini, C., Bagella, L., D'Andrilli, G., Masciullo, V., Romano, G., Scambia, G., Zupi, G., Giordano, A. Clin. Cancer Res. (2004) [Pubmed]
  10. Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer. Caputi, M., Groeger, A.M., Esposito, V., De Luca, A., Masciullo, V., Mancini, A., Baldi, F., Wolner, E., Giordano, A. Clin. Cancer Res. (2002) [Pubmed]
  11. Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells. Xu, X., Kang, S.H., Heidenreich, O., Okerholm, M., O'Shea, J.J., Nerenberg, M.I. J. Clin. Invest. (1995) [Pubmed]
  12. CrkI adapter protein modulates cell migration and invasion in glioblastoma. Takino, T., Nakada, M., Miyamori, H., Yamashita, J., Yamada, K.M., Sato, H. Cancer Res. (2003) [Pubmed]
  13. Molecular heterogeneity at the breakpoints of smaller 20q deletions. Hollings, P.E. Genes Chromosomes Cancer (1994) [Pubmed]
  14. Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence. Litovchick, L., Chestukhin, A., DeCaprio, J.A. Mol. Cell. Biol. (2004) [Pubmed]
  15. E2F-5, a new E2F family member that interacts with p130 in vivo. Hijmans, E.M., Voorhoeve, P.M., Beijersbergen, R.L., van 't Veer, L.J., Bernards, R. Mol. Cell. Biol. (1995) [Pubmed]
  16. 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]
  17. Mutations in the retinoblastoma-related gene RB2/p130 in adult T-cell leukaemia/lymphoma. Takeuchi, S., Takeuchi, N., Tsukasaki, K., Fermin, A.C., De Vas, S., Seo, H., Koeffler, H.P. Leuk. Lymphoma (2003) [Pubmed]
  18. Genetic alterations disrupting the nuclear localization of the retinoblastoma-related gene RB2/p130 in human tumor cell lines and primary tumors. Cinti, C., Claudio, P.P., Howard, C.M., Neri, L.M., Fu, Y., Leoncini, L., Tosi, G.M., Maraldi, N.M., Giordano, A. Cancer Res. (2000) [Pubmed]
  19. 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]
  20. SV40 large T antigen promotes dephosphorylation of p130. Lin, J.Y., DeCaprio, J.A. J. Biol. Chem. (2003) [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. Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter. Araki, K., Nakajima, Y., Eto, K., Ikeda, M.A. Oncogene (2003) [Pubmed]
  24. The E7 proteins of low- and high-risk human papillomaviruses share the ability to target the pRB family member p130 for degradation. Zhang, B., Chen, W., Roman, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B cells. A role for p59(Fyn) and SHP2. Manié, S.N., Astier, A., Haghayeghi, N., Canty, T., Druker, B.J., Hirai, H., Freedman, A.S. J. Biol. Chem. (1997) [Pubmed]
  26. Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130 repressor complex in transgenic mice in vivo. Bouzahzah, B., Fu, M., Iavarone, A., Factor, V.M., Thorgeirsson, S.S., Pestell, R.G. Cancer Res. (2000) [Pubmed]
  27. Intranuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. Smith-McCune, K., Kalman, D., Robbins, C., Shivakumar, S., Yuschenkoff, L., Bishop, J.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation. Wang, S., Ghosh, R.N., Chellappan, S.P. Mol. Cell. Biol. (1998) [Pubmed]
  29. 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]
  30. E2F4 regulates a stable G(2) arrest response to genotoxic stress in prostate carcinoma. Crosby, M.E., Jacobberger, J., Gupta, D., Macklis, R.M., Almasan, A. Oncogene (2007) [Pubmed]
  31. 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]
  32. Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7. Sterner, J.M., Dew-Knight, S., Musahl, C., Kornbluth, S., Horowitz, J.M. Mol. Cell. Biol. (1998) [Pubmed]
  33. The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1. Kong, L.J., Meloni, A.R., Nevins, J.R. Mol. Cell (2006) [Pubmed]
  34. 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]
  35. pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis. Russo, G., Claudio, P.P., Fu, Y., Stiegler, P., Yu, Z., Macaluso, M., Giordano, A. Oncogene (2003) [Pubmed]
  36. Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo. Howard, C.M., Claudio, P.P., Gallia, G.L., Gordon, J., Giordano, G.G., Hauck, W.W., Khalili, K., Giordano, A. J. Natl. Cancer Inst. (1998) [Pubmed]
 
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