Disease relevance of Rb1

• Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation [1].
• Reductions in cyclin-dependent kinase (CDK)2 (82%) and CDK4 (77%) kinase activity in ER carcinomas were likely to account for the observed effects on retinoblastoma and E2F-1 [2].
• Similarly, murine S49 lymphoma cells, which, like SAOS2 cells, lack Rb, require the N-terminal activation domain for growth arrest and induce CDI expression upon GR activation [3].
• In this study, we attempted to determine the effects of ginsenosides Rb1 and Rg1 in a rat model, with specific emphasis on nitric oxide and cytokines, which have been implicated in chronic brain inflammation [4].
• In conclusion, neurodegenerative diseases such as Alzheimer's disease, which is caused primarily by cell death due to chronic inflammation and cell stress, might be controlled by proper doses of non-toxic, natural Rg1 and Rb1 [4].

Psychiatry related information on Rb1

• The ability of Rb1 to prevent memory deficits may be related to facilitation of ACh metabolism in the central nervous system [5].
• The effect of ginsenoside Rg1 and Rb1 on memory in mice and rats were studied using one trial avoidance learning method [6].
• Alternatively, members of the Id family, for example, Id 2 can also bind to non-bHLH proteins such as retinoblastoma (Rb) and ETS-TCF to modulate their activities [7].

High impact information on Rb1

• The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes [8].
• LNA-1 overcame the flat-cell phenotype induced by retinoblastoma protein in Saos2 cells [9].
• These results indicate that there is an additional mechanism by which Rb suppresses cell growth, namely that Rb directly represses transcription of the rRNA genes [10].
• The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro [11].
• In Rat-1 cells, the phosphorylation-site-mutated (PSM)-RB, but not wild-type RB, can inhibit S-phase entry [12].

Chemical compound and disease context of Rb1

• One ginsenoside, Rb1, extracted from North American ginseng (Panax quinquefolium L.), partially prevents the memory deficits induced by a cholinergic agent (scopolamine) in rats [5].
• Relationship of polymorphisms near the rat prolactin, N-ras, and retinoblastoma genes with susceptibility to estrogen-induced pituitary tumors [13].
• We have observed restriction fragment length polymorphisms for the N-ras and retinoblastoma (Rb) genes between rat strains that are susceptible or resistant to induction of pituitary tumors by diethylstilbestrol (DES) [14].
• Differential requirements for ras and the retinoblastoma tumor suppressor protein in the androgen dependence of prostatic adenocarcinoma cells [15].
• Alterations of the retinoblastoma-related gene RB2/p130 in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats [16].

Biological context of Rb1

• Epidermal growth factor-induced rapid retinoblastoma phosphorylation at Ser780 and Ser795 is mediated by ERK1/2 in small intestine epithelial cells [17].
• The retinoblastoma protein Rb is critical for the regulation of mammalian cell cycle entry [17].
• Both RB and RB2/P130 decreased cell proliferation rate [18].
• To this end, we ectopically expressed either RB or RB2/p130 and monitored proliferation, differentiation and apoptosis in rat primary MSC cultures induced to differentiate toward the neuron-like phenotype [18].
• Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication [19].

Anatomical context of Rb1

• Beta-escin treatment in HT-29 cells induced growth arrest at the G1-S phase, which was associated with the induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and this correlated with reduced phosphorylation of retinoblastoma protein [20].
• We examined the relationship between mitogen-activated MEK (mitogen and extracellular signal-regulated protein kinase kinase) and phosphorylation of the gene product encoded by retinoblastoma (hereafter referred to as Rb) in vascular smooth muscle cells [21].
• In vivo expression patterns of MyoD, p21, and Rb proteins in myonuclei and satellite cells of denervated rat skeletal muscle [22].
• Denervation induced MyoD expression in myonuclei and satellite cell nuclei, whereas p21 and Rb were found only in myonuclei [22].
• Ras-regulated hypophosphorylation of the retinoblastoma protein mediates neuronal differentiation in PC12 cells [23].

Associations of Rb1 with chemical compounds

• Mitogen-induced rapid phosphorylation of serine 795 of the retinoblastoma gene product in vascular smooth muscle cells involves ERK activation [21].
• Incorporation of EPA or DHA into SMC, which are then activated by interleukin-1beta to mimic inflammation, decreases promoter activity of the cyclin D1 gene and phosphorylation of the retinoblastoma protein [24].
• On the expression of cell cycle regulatory proteins, ferulic acid elevated the protein content of p21(waf1/cip1), decreased expression of cyclin D1 and inhibited phosphorylation of retinoblastoma protein, suggesting that ferulic acid inhibited VSMC proliferation by regulating the cell progression from G1 to S phase [25].
• Furthermore, inostamycin also inhibited cyclin D1 expression induced by serum; and consequently, hyperphosphorylation of retinoblastoma protein (pRB) by RB-kinases such as CDK4 and CDK2 was abolished, which would result in elimination of functional inactivation of pRB [26].
• The present study determined, in vitro, the effect of angiotensin II (Ang II) treatment of neonatal rat cardiac myocytes on protein levels of cyclins and retinoblastoma gene product (pRb) phosphorylation [27].

Physical interactions of Rb1

• In vitro studies show that Rb1 has no effect on quinuclidinyl benzylate binding or on acetylcholinesterase activity, but facilitates the release of acetylcholine (ACh) from hippocampal slices [5].
• We recently demonstrated that the AhR interacts with the retinoblastoma protein (pRb) [28].
• Thus multiple pathways leading to activation of NFkappaB, SP-1, Ets, AP-1, and retinoblastoma binding factors in tumor cells all may contribute to MMP-9 transcription and hence to metastasis [29].

Enzymatic interactions of Rb1

• Decreased p27 was correlated with increased levels of Cdk2 and increased levels of phosphorylated retinoblastoma protein [30].

Regulatory relationships of Rb1

• The principal function of TFIIIB is to recruit pol III to its cognate gene template, an activity that is known to be inhibited by RB and stimulated by ERK [31].
• Peroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1--> S transition in vascular smooth muscle cells [32].
• Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells [33].
• TGF-beta 1 inhibits DNA synthesis and phosphorylation of the retinoblastoma gene product in a rat liver epithelial cell line [34].
• Identification and characterization of the putative retinoblastoma control element of the rat insulin-like growth factor binding protein-2 gene [35].

Other interactions of Rb1

• Following HGF treatment retinoblastoma protein (pRB) was present in the hypophosphorylated state [36].
• However, hypoxic conditions cause TFIIIB dissociation from c-Myc and ERK, at the same time as increasing its interaction with RB [31].
• Using immunohistochemical approaches, we characterized cell types expressing MyoD, p21, and Rb and the relationship among these factors in the myonucleus of denervated muscles [22].
• Forskolin significantly enhanced heregulin-stimulated expression of cyclin D and phosphorylation of the retinoblastoma gene product [37].
• For the above reasons, RB and RB2/P130 may have a role in neural differentiation but not in neural determination [38].

Analytical, diagnostic and therapeutic context of Rb1

• Molecular analysis of neural differentiation markers and immunocytochemistry revealed that RB2/p130 contributes mainly to the induction of generic neural properties and RB triggers cholinergic differentiation [18].
• In addition, we quantitatively examined the time course changes and expression patterns among distinct myofiber types of MyoD, p21, and Rb during denervation [22].
• A cDNA of the rat retinoblastoma gene (RB) was prepared from total RNA of rat liver using reverse transcription-polymerase chain reaction (RT-PCR) [39].
• As determined by appropriate combinations of immunoprecipitations, Western blots, and kinase activity assays, it was found that levels of phosphorylated retinoblastoma and E2F-1 were significantly reduced by ER (approximately 40 and 75%, respectively; P < 0.01), an effect that was partially reversed by ER-REP [2].
• Western blot analysis showed that onychin inhibited Rb phosphorylation and reduced the expression of cyclin D1 and cyclin E. The effects of onychin on proliferation, the cell cycle and the expression of cyclins in VSMCs were similar to those of genistein, an inhibitor of tyrosine kinase [40].

References