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    The retinoblastoma family: Twins or distant cousins?

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    Name:
    The retinoblastoma family twins ...
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    Genre
    Review
    Journal
    Date
    2002-09-23
    Author
    Claudio, PP
    Tonini, T
    Giordano, A
    Subject
    Animals
    Apoptosis
    Cell Differentiation
    Chromosome Mapping
    Evolution, Molecular
    Genes, Retinoblastoma
    Humans
    Mice
    Neovascularization, Physiologic
    Nuclear Proteins
    Phosphoproteins
    Phylogeny
    Plants
    Proteins
    Rats
    Retinoblastoma Protein
    Retinoblastoma-Like Protein p107
    Retinoblastoma-Like Protein p130
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    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5089
    
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    DOI
    10.1186/gb-2002-3-9-reviews3012
    Abstract
    The destiny of a cell - whether it undergoes division, differentiation or death - results from an intricate balance of many regulators, including oncoproteins, tumor-suppressor proteins and cell-cycle-associated proteins. One of the better-studied tumor suppressors is the retinoblastoma protein, known as pRb or p105. Two recently identified proteins, pRb2/p130 and p107, show structural and functional similarities to pRb, and these proteins and their orthologs make up the retinoblastoma (Rb) family. Members of the family have been found in animals and plants, and a related protein is known in the alga Chlamydomonas. Members of the Rb family are bound and inactivated by viral proteins and, in turn, bind cellular transcription factors and repress their function, and can also form complexes with cyclins and cyclin-dependent kinases and with histone deacetylases. The are found in the nucleus and their subnuclear localization depends on binding to the nuclear matrix. Members of the family form part of a signal-transduction pathway called the Rb pathway, which is important in cell-cycle regulation and have roles in growth suppression, differentiation and apoptosis in different organisms and cell types.
    Citation to related work
    Springer Science and Business Media LLC
    Has part
    Genome Biology
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    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/5071
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      Role of Retinoblastoma Protein Family (Rb/p105 and Rb2/p130) Expression in the Histopathological Classification of Borderline Ovarian Tumors

      Masciullo, V; Valdivieso, P; Amadio, G; Santoro, A; Angelico, G; Sgambato, A; Boffo, S; Giordano, A; Scambia, G; Zannoni, GF; Giordano, Antonio|0000-0002-5959-016X; Boffo, Silvia|0000-0002-6352-160X (2020-11-11)
      © Copyright © 2020 Masciullo, Valdivieso, Amadio, Santoro, Angelico, Sgambato, Boffo, Giordano, Scambia and Zannoni. Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. The identification of valuable markers for the diagnosis and classification of these tumors is in need. Among the molecular candidates, the Retinoblastoma (Rb) family members Rb/p105 and Rb2/p130 seem to play a pivotal role in ovarian cancer. In particular, Rb/p105, when in the unphosphorylated form, acts as a growth suppressor controlling cell cycle and tumor progression; whereas, the phosphorylated form activates gene transcription and cellular proliferation. While Rb/p105 is ubiquitously confined to the nuclei of cycling and quiescent cells, Rb2/p130 activity is also regulated by intracellular localization. According to this, Rb family members could represent a novel marker in diagnosis and classification risk for patients with BOT. In this study, we evaluated the expression and subcellular localization of proteins of the retinoblastoma (Rb) gene family in 65 ovarian borderline tumors. Statistically significant differences were found in nuclear and cytoplasmic expressions of Rb/p105 and Rb2/p130 according to different examined histotypes. In detail, the nuclear expression of Rb/p105 and Rb2/p130 was more frequently detected in serous (84.6%) than sero-mucinous (42.1%) and mucinous (50%) types. Conversely, the cytoplasmic expression of Rb2/p130 was not detected in serous tumors and frequently observed in mucinous subtypes (80%). Our findings suggest that Rb proteins do not play a key role in the tumor progression of serous borderline tumors since any cases showed cytoplasmic localization. By contrast, the observed higher cytoplasmic expression of Rb2/p130 in intestinal mucinous BOTs is indicative of Rb protein family involvement in the cancerogenesis pathway of mucinous ovarian tumors. Also, mucinous BOTs of intestinal-type, exhibiting low nuclear and high cytoplasmic levels of Rb2/p130 might potentially be considered a high-risk category of malignant evolution. Further studies on larger series are needed to clarify how BOTs could be stratified in different prognostic groups according to their Rb proteins immunohistochemical profile.
    • Thumbnail

      Misidentified Human Gene Functions with Mouse Models: The Case of the Retinoblastoma Gene Family in Senescence

      Alessio, N; Capasso, S; Ferone, A; Di Bernardo, G; Cipollaro, M; Casale, F; Peluso, G; Giordano, A; Galderisi, U; Giordano, Antonio|0000-0002-5959-016X (2017-10-01)
      © 2017 The Authors Although mice models rank among the most widely used tools for understanding human genetics, biology, and diseases, differences between orthologous genes among species as close as mammals are possible, particularly in orthologous gene pairs in which one or more paralogous (i.e., duplicated) genes appear in the genomes of the species. Duplicated genes can possess overlapping functions and compensate for each other. The retinoblastoma gene family demonstrates typical composite functionality in its three member genes (i.e., RB1, RB2/P130, and P107), all of which participate in controlling the cell cycle and associated phenomena, including proliferation, quiescence, apoptosis, senescence, and cell differentiation. We analyzed the role of the retinoblastoma gene family in regulating senescence in mice and humans. Silencing experiments with each member of the gene family in mesenchymal stromal cells (MSCs) and fibroblasts from mouse and human tissues demonstrated that RB1 may be indispensable for senescence in mouse cells, but not in human ones, as an example of species specificity. Furthermore, although RB2/P130 seems to be implicated in maintaining human cell senescence, the function of RB1 within any given species might differ by cell type, as an example of cell specificity. For instance, silencing RB1 in mouse fibroblasts induced a reduced senescence not observed in mouse MSCs. Our findings could be useful as a general paradigm of cautions to take when inferring the role of human genes analyzed in animal studies and when examining the role of the retinoblastoma gene family in detail.
    • Thumbnail

      Silencing human Rb2/p130 with shRNA

      Leucci, E; Onnis, A; De Falco, G; Luzzi, A; Cerino, G; Giordano, A; Leoncini, L; Giordano, Antonio|0000-0002-5959-016X (2007-06-07)
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