RB's original CIN?

Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
Genes & development (Impact Factor: 10.8). 07/2010; 24(13):1329-33. DOI: 10.1101/gad.1948010
Source: PubMed


The retinoblastoma tumor suppressor RB is the downstream mediator of a cellular pathway that is thought to prevent cancer by controlling the ability of cells to enter or exit the cell cycle in G0/G1. Recently, however, accumulating evidence has suggested that RB, its family members p107 and p130, and their partners, the E2F family of transcription factors, may have important cellular functions beyond the G1/S transition of the cell cycle, including during DNA replication and at the transition into mitosis. In this issue of Genes & Development, three studies demonstrate a critical role for RB in proper chromosome condensation, centromeric function, and chromosome stability in mammalian cells, and link these cellular functions of RB to tumor suppression in mice. Here we discuss how transcriptional and post-transcriptional mechanisms under the control of the RB pathway ensure accurate progression through mitosis, thereby preventing cancer development.

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Available from: Julien Sage,
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    • "Retinoblastoma (Rb) is a tumor suppressor gene playing important role in cell cycle regulation in proliferation, apoptosis, and neuron survival [37]–[41]. In proliferating cells, cyclins/CDKs could phosphorylate Rb protein, which in turn acts as a transcriptional factor and regulates its downstream gene expression for cell cycle process [42]. "
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    ABSTRACT: Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.
    PLoS ONE 03/2014; 9(3):e90850. DOI:10.1371/journal.pone.0090850 · 3.23 Impact Factor
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    • "It was one of the first tumor suppressor genes identified and is commonly inactivated in several tumor types (Marshall, 1991). It is common for tumors with inactivating mutations in pRB to be aneuploid with an increased susceptibility to changes in DNA ploidy (Isaac et al., 2006; Mayhew et al., 2007; Srinivasan et al., 2007; Amato et al., 2009a,b), and recent reports have shown that pRB influences mitosis through a function that is independent of its role in cell cycle progression (Sage and Straight, 2010). The E2F transcription factor family proteins are downstream targets that are negatively regulated by pRB. "
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    ABSTRACT: Most solid tumors are characterized by abnormal chromosome numbers (aneuploidy) and karyotypic profiling has shown that the majority of these tumors are heterogeneous and chromosomally unstable. Chromosomal instability (CIN) is defined as persistent mis-segregation of whole chromosomes and is caused by defects during mitosis. Large-scale genome sequencing has failed to reveal frequent mutations of genes encoding proteins involved in mitosis. On the contrary, sequencing has revealed that most mutated genes in cancer fall into a limited number of core oncogenic signaling pathways that regulate the cell cycle, cell growth, and apoptosis. This led to the notion that the induction of oncogenic signaling is a separate event from the loss of mitotic fidelity, but a growing body of evidence suggests that oncogenic signaling can deregulate cell cycle progression, growth, and differentiation as well as cause CIN. These new results indicate that the induction of CIN can no longer be considered separately from the cancer-associated driver mutations. Here we review the primary causes of CIN in mitosis and discuss how the oncogenic activation of key signal transduction pathways contributes to the induction of CIN.
    Frontiers in Oncology 06/2013; 3:164. DOI:10.3389/fonc.2013.00164
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    • "Another protein, the retinoblastoma (RB) tumour suppressor, has been also related to CIN. RB tumour suppressor is the downstream mediator of a cellular pathway that is thought to prevent cancer by controlling the ability of cells to enter or exit the cell cycle in G 0 /G 1 [38]. "
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    ABSTRACT: Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.
    11/2012; 2012(1):139268. DOI:10.5402/2012/139268
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