Abstract:
:Transcription factor E2F plays an important role in coordinating and integrating early cell cycle progression with the transcription apparatus. It is known that physiological E2F arises when a member of two families of proteins, E2F and DP, interact as E2F/DP heterodimers and that transcriptional activity is regulated through the physical association of pocket proteins such as pRb. However, little information is available regarding the mechanisms which control the levels of functional E2F. In this study, we have characterised one such mechanism which regulates the nuclear accumulation and activity of E2F. Specifically, we show that E2F proteins fall into two distinct categories according to their ability to accumulate in nuclei, one being exemplified by E2F-1 and the other by E2F-4 and -5. Thus, E2F-1 possesses an intrinsic nuclear localization signal whereas E2F-4 and -5 are devoid of such a signal. Furthermore, we find for E2F-4 and -5 that two distinct processes govern their nuclear accumulation whereby the nuclear localization signal is supplied in trans from either a DP heterodimer partner or a physically associated pocket protein. It is consistent with the role of pocket proteins in regulating nuclear accumulation that we find E2F-5 to be nuclear during early cell cycle progression with an increased cytoplasmic concentration in cycling cells. Our data show that the mechanism of nuclear accumulation determines the functional consequence of E2F on cell cycle progression: pocket protein-mediated accumulation impedes cell cycle progression, whereas DP-regulated nuclear accumulation promotes cell cycle progression. Moreover, the inactivation of pocket proteins by the adenovirus Ela protein, and subsequent release of E2F, failed to displace nuclear E2F. Our study identifies a new level of regulation in the control of E2F activity exerted at the level of nuclear accumulation where subunit composition and interaction with pocket proteins dictates the functional consequence on cell cycle progression.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Allen KE,de la Luna S,Kerkhoven RM,Bernards R,La Thangue NBsubject
Has Abstractpub_date
1997-11-01 00:00:00pages
2819-31eissn
0021-9533issn
1477-9137journal_volume
110 ( Pt 22)pub_type
杂志文章abstract::Immunofluorescent anti-tubulin staining has been used to follow nuclear progression from dictyate to metaphase II during meiotic maturation of mouse oocytes in vitro. Antibody directed against tubulin isolated from sea-urchin eggs decorates the metaphase I and metaphase II spindles, as well as the cytoplasmic bridge, ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2017-07-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01504
更新日期:2004-11-15 00:00:00
abstract::Asymmetric cell division can produce daughter cells with different developmental fates and is often accompanied by a difference in cell size. A number of recent genetic and in vivo imaging studies in Drosophila and Caenorhabditis elegans have begun to elucidate the mechanisms underlying the rearrangements of the cytos...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
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更新日期:2002-06-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2017-06-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.136176
更新日期:2013-12-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01302
更新日期:2004-08-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.150888
更新日期:2014-07-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.02856
更新日期:2006-02-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.03081
更新日期:2006-09-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.122606
更新日期:2013-08-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2013-02-15 00:00:00
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journal_title:Journal of cell science
pub_type: 评论,杂志文章,评审
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pub_type: 杂志文章
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doi:10.1242/jcs.255422
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
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journal_title:Journal of cell science
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.128009
更新日期:2014-10-01 00:00:00
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journal_title:Journal of cell science
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更新日期:2010-04-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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更新日期:2000-03-01 00:00:00
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pub_type: 杂志文章
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