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

• Levels of Rb2/p130 protein are increased 5-10-fold following all-trans-retinoic acid (ATRA) treatment of the retinoid-sensitive ovarian adenocarcinoma cell line CAOV3, but not the retinoid-resistant adenocarcinoma cell line SKOV3 [8].
• The purpose of this study is to investigate the possible role of pRb2/p130 in the sensitivity of ovarian cancer to camptothecin, doxorubicin, and taxol [9].
• We developed an immunohistochemical assay suitable for the detection of pRb2/p130, the last discovered member of the retinoblastoma gene family, on formalin-fixed and paraffin-embedded sections [10].
• Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines [11].
• Expression of CrkI but not CrkII in glioblastoma U87MG cells induced transformation that stimulated cell migration and invasion concomitant with tyrosine phosphorylation of p130 Crk-associated substrate [12].

Biological context of RBL2

• 1. A candidate tumor suppressor gene, RBL2, and the SRC oncogene were both located within the commonly deleted region [13].
• Regulation of p130 by GSK3 provides a novel link between growth factor signaling and regulation of the cell cycle progression and exit [14].
• Phosphorylation of p130 by GSK3 contributes to the stability of p130 but does not affect its ability to interact with E2F4 or cyclins [14].
• Recently, a cDNA encoding a third member of the retinoblastoma gene family, p130, was isolated. p130 also interacts with E2F DNA binding activity, primarily in the G0 phase of the cell cycle [15].
• The retinoblastoma (pRb), p107, and p130 pocket proteins bind to the E2F transcription factors to control gene expression [16].

Anatomical context of RBL2

• Mutations in the retinoblastoma-related gene RB2/p130 in adult T-cell leukaemia/lymphoma [17].
• Only the lymphoid cell lines showed an abnormal cytoplasmic localization of pRb2/p130, suggesting possible alterations within the region of nuclear localization signaling [18].
• Genetic alterations disrupting the nuclear localization of the retinoblastoma-related gene RB2/p130 in human tumor cell lines and primary tumors [18].
• 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 [19].
• Here we describe the use of a cell-free system to characterize the effect of T Ag on p130 phosphorylation [20].

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

• The "pocket proteins" pRb (retinoblastoma tumor suppressor protein), p107, and p130 regulate cell proliferation via phosphorylation-sensitive interactions with E2F transcription factors and other proteins [21].
• Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107 [31].
• The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA replication assay system [32].
• The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1 [33].
• TGF-beta1 treatment enhanced p130 binding to the cdc25A promoter E2F site assessed in chromatin immunoprecipitation assays [26].

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