Synthetic Lethality of Retinoblastoma Mutant Cells in the Drosophila Eye by Mutation of a Novel Peptidyl Prolyl Isomerase Gene (original) (raw)
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Retinoblastoma protein family in cell cycle and cancer: a review
Journal of cellular …, 1996
Two genes, p707 and Rb2/p730, are strictly related to RB, the most investigated tumor suppressor gene, responsible for susceptibility to retinoblastoma. The products of these three genes, namely pRb, pl07, and pRb2/pl30 are characterized by a peculiar steric conformation, called "pocket," responsible for most of the functional interactions characterizing the activity of these proteins in the homeostasis of the cell cycle. The interest in these genes and proteins springs from their ability to regulate cell cycle processes negatively, being able, for example, to dramatically slow down neoplastic growth. So far, among these genes, only RB is firmly established to act as a tumor suppressor, because its lack-of-function is clearly involved in tumor onset and progression. It has been found deleted or mutated in most retinoblastomas and sarcomas, but its inactivation is likely to play a crucial role in other types of human cancers. The two other members of the family have been discovered more recently and are currently under extensive investigation. We review analogies and differences among the pocket protein family members, in an attempt to understand their functions in normal and cancer cells. ri-1996 WiIey-Liss, Inc.
Retinoblastoma: the disease, gene and protein provide critical leads to understand cancer
Seminars in Cancer Biology, 2000
Retinoblastoma has contributed much to the understanding of cancer. The protein product of the RB gene, pRB, is a multifaceted regulator of transcription which controls the cell cycle, differentiation and apoptosis in normal development of specific tissues. Elucidating the mechanisms in which pRB plays a critical role will enable novel therapies and strategies for prevention, not only for retinoblastoma, but for cancer in general.
Distinct developmental expression of Drosophila retinoblastoma factors
Gene Expression Patterns, 2005
Retinoblastoma (RB) tumor suppressor proteins are important regulators of the cell cycle and are implicated in a wide variety of human tumors. Genetic analysis of RB mutations in humans and in model systems indicates that individual RB proteins also have distinct functions in development. Specific target genes or mechanisms of action of individual RB proteins in developmental contexts are not well understood, however. To better understand the developmental activities of the two RB family members in Drosophila, we have characterized endogenous expression patterns of Rbf1 and Rbf2 proteins and transcripts in embryos and imaginal discs. These gene products are coexpressed at several stages of development, however, spatial and temporal differences are evident, including partly complementary patterns of expression in the embryonic central nervous system.
Disruption of the Pp1-87B Gene Stimulates Tumor Formation in the Eye of Drosophila
Annual Research & Review in Biology
Protein phosphatases are a set of enzymes in charge of the dephosphorylation of several proteins and enzymes in a cell. Dephosphorylation process is essential for organizing a huge number of cellular actions. In Drosophila, protein phosphatase 1 at B87 (Pp1-87B) gene encodes one of the four variants of the protein phosphatase 1 catalytic subunit and located on chromosome number three of Drosophila melanogaster. In this proposal, Pp1-87B mutation carrying lethal P-element insertions at a third chromosome of Drosophila melanogaster was screened to study the possible of this gene as tumor suppressor gene. Disruption of the genetic sequence of Pp1-87B gene can produce mutant phenotypes in the large clone mosaic eyes. The mutant eyes have either a rough or cell lethal phenotype which indicates the disrupted gene is essential for proper eye development. Further analysis of the mechanism by which these disrupted gene function may offer useful information for cancer studies. To study if the obtained set of Drosophila P-element mutations have Original Research Article
The Retinoblastoma Gene: A Prototypic and Multifunctional Tumor Suppressor
Experimental Cell Research, 2001
Genome instability has been implicated in the generation of multiple somatic mutations that underlie cancer. Germline mutation in the retinoblastoma (RB) gene leads to tumor formation in both human and experimental animal models, and reintroduction of wild-type RB is able to suppress neoplastic phenotypes. Rb governs the passage of cells through the G1 phase-restriction point and this control is lost in most cancer cells. Rb has also been shown to promote terminal differentiation and prevent cell cycle reentry. Recent studies implicate Rb in mitotic progression, faithful chromosome segregation, checkpoint control, and chromatin remodeling, suggesting that Rb may function in the maintenance of genome integrity. It is likely that Rb suppresses tumor formation by virtue of its multiple biological activities. A single protein capable of performing multiple antioncogenic functions may be a common characteristic of other tumor suppressors including p53 and BRCA1/2.
The retinoblastoma tumor-suppressor gene, the exception that proves the rule
Oncogene, 2006
The retinoblastoma tumor-suppressor gene (Rb1) is centrally important in cancer research. Mutational inactivation of Rb1 causes the pediatric cancer retinoblastoma, while deregulation of the pathway in which it functions is common in most types of human cancer. The Rb1-encoded protein (pRb) is well known as a general cell cycle regulator, and this activity is critical for pRbmediated tumor suppression. The main focus of this review, however, is on more recent evidence demonstrating the existence of additional, cell type-specific pRb functions in cellular differentiation and survival. These additional functions are relevant to carcinogenesis suggesting that the net effect of Rb1 loss on the behavior of resulting tumors is highly dependent on biological context. The molecular mechanisms underlying pRb functions are based on the cellular proteins it interacts with and the functional consequences of those interactions. Better insight into pRb-mediated tumor suppression and clinical exploitation of pRb as a therapeutic target will require a global view of the complex, interdependent network of pocket protein complexes that function simultaneously within given tissues.
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1992
Mutational inactivation of the retinoblastoma gene (RB) is an invariant feature of the childhood eye cancer retinoblastoma and of tumor cells derived therefrom. In a previous study, retrovirus-mediated transfer of wild-type RB into cultured retinoblastoma cells resulted in a marked enlargement and reduced growth rate of these cells, as well as loss of their tumorigenic properties in nude mice. It was therefore difficult to separate the proposed growth-suppressing and tumor-suppressing activities of RB protein. Here, we show that clones of RB-reconstituted retinoblastoma cells can be isolated that stably express apparently normal RB protein for at least 20 months of continuous culture. These clones were indistinguishable from nonreconstituted cells by multiple parameters including morphology, growth rate, and cell cycle distribution. Despite similar phenotypes in culture, clones with stable RB expression were uniformly nontumorigenic in nude mice, whereas those that lost such express...