Abstract:
:Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and thereby inhibiting cellular differentiation. To examine the effect of Id-2 on cell proliferation, we overexpressed Id-2 in the human osteosarcoma cell line U2OS. Id-2 expression in U2OS reduced the serum requirement for growth and stimulated cellular proliferation by shortening the doubling time and increasing the percentage of cells in S phase. We demonstrated that Id-2 expression was able to reverse the inhibition of cellular proliferation and the block in cell cycle progression mediated by the product of the retinoblastoma tumor suppressor gene pRB. This effect was not associated with changes in the state of pRb phosphorylation in transfected cells. In vitro, unphosphorylated pRb from cell lysates specifically bound Id-2 but was not able to bind a mutated form of Id-2 lacking the HLH domain that also did not antagonize the growth arrest by pRb. In vitro-synthesized pRb containing mutations within the E1A/large T-binding pocket did not bind Id-2. However, wild-type pRb was able to bind to a region of Id-2 corresponding to only the HLH domain. In vivo, a physical association between Id-2 and pRb was seen in cross-linked extracts from SAOS-2 cells transfected with Id-2 and pRb. Our data identify a role for Id-2 in the regulation of cellular proliferation and suggest that the interaction between Id-2 and pRB is a molecular pathway over which synchronous changes in growth and differentiation are mediated in vivo.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Iavarone A,Garg P,Lasorella A,Hsu J,Israel MAdoi
10.1101/gad.8.11.1270subject
Has Abstractpub_date
1994-06-01 00:00:00pages
1270-84issue
11eissn
0890-9369issn
1549-5477journal_volume
8pub_type
杂志文章abstract::The unique property of stem cells to self-renew suggests specific mechanisms that regulate their cell-cycle progression. In the present study, we identify a novel protein, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.55671
更新日期:2002-12-01 00:00:00
abstract::Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the mol...
journal_title:Genes & development
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abstract::The structurally related POU homeo domain proteins Pit-1 and Oct-2 activate pituitary- and lymphoid-specific transcription, respectively, by binding to similar AT-rich motifs in their target genes. In this study we identify bases critical for recognition and activation by Pit-1 and examine how small differences in Pit...
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journal_title:Genes & development
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doi:10.1101/gad.1009002
更新日期:2002-09-15 00:00:00
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journal_title:Genes & development
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更新日期:2007-05-01 00:00:00
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journal_title:Genes & development
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pub_type: 评论,杂志文章
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abstract::We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knocko...
journal_title:Genes & development
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更新日期:2008-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2004-12-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.201301
更新日期:2001-09-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1121403
更新日期:2003-09-15 00:00:00
abstract::Small noncoding RNAs, including small interfering RNAs (siRNAs) and micro RNAs (miRNAs) of approximately 21 nucleotides (nt) in length, have emerged as potent regulators of gene expression at both transcriptional and post-transcriptional levels in diverse organisms. Here we report the identification of a novel class o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1434406
更新日期:2006-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.12.1400
更新日期:1994-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1408106
更新日期:2006-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.184705.111
更新日期:2012-03-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1636408
更新日期:2008-03-15 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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更新日期:1991-06-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1999-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2000-01-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.870801
更新日期:2001-03-15 00:00:00
abstract::A prominent feature of cell differentiation is the initiation and maintenance of an irreversible cell cycle arrest with the complex involvement of the retinoblastoma (RB) family (RB, p130, p107). We have isolated the HBP1 transcriptional repressor as a potential target of the RB family in differentiated cells. By homo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.3.383
更新日期:1997-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.287404
更新日期:2004-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1995-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1996-07-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1553007
更新日期:2007-08-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00