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    Subnuclear organization and trafficking of regulatory proteins: implications for biological control and cancer

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    Authors
    Stein, Gary S.
    Van Wijnen, Andre J.
    Stein, Janet L.
    Lian, Jane B.
    Montecino, Martin A.
    Zaidi, Kaleem
    Javed, Amjad
    UMass Chan Affiliations
    Department of Cell Biology and Cancer Center
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2001-06-05
    Keywords
    Animals; Cell Nucleus; *Gene Expression Regulation; Humans; Leukemia; Models, Biological; Neoplasms; Transcription Factors
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1002/1097-4644(2000)79:35+<84::AID-JCB1130>3.0.CO;2-9
    Abstract
    The regulated and regulatory components that interrelate nuclear structure and function must be experimentally established. A formidable challenge is to define further the control of transcription factor targeting to acceptor sites associated with the nuclear matrix. It will be important to determine whether acceptor proteins are associated with a pre-existing core-filament structural lattice or whether a compositely organized scaffold of regulatory factors is dynamically assembled. An inclusive model for all steps in the targeting of proteins to subnuclear sites cannot yet be proposed. However, this model must account for the apparent diversity of intranuclear targeting signals. It is also important to assess the extent to which regulatory discrimination is mediated by subnuclear domain-specific trafficking signals. Furthermore, the checkpoints that monitor subnuclear distribution of regulatory factors and the sorting steps that ensure both structural and functional fidelity of nuclear domains in which replication and expression of genes occur must be biochemically and mechanistically defined. There is emerging recognition that placement of regulatory components of gene expression must be temporally and spatially coordinated to facilitate biological control. The consequences of breaches in nuclear structure-function relationships are observed in an expanding series of diseases that include cancer [Weis et al., 1994; Rogaia et al., 1997; Yano et al., 1997; Rowley, 1998; Zeng et al., 1998; McNeil et al., 1999; Tao and Levine, 1999a] and neurological disorders [Skinner et al., 1997]. As the repertoire of architecture-associated regulatory factors and cofactors expands, workers in the field are becoming increasingly confident that nuclear organization contributes significantly to control of transcription. To gain increased appreciation for the complexities of subnuclear organization and gene regulation, we must continue to characterize mechanisms that direct regulatory proteins to specific transcription sites within the nucleus so that these proteins are in the right place at the right time. J. Cell. Biochem. Suppl. 35:84-92, 2000.
    Source
    J Cell Biochem Suppl. 2000;Suppl 35:84-92.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32629
    PubMed ID
    11389536
    Related Resources
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    Morningside GSBS Scholarly Publications

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