Abstract：
:The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosine kinase. The large A/B pocket and the C pocket are shown here to be functionally distinct and can be occupied simultaneously. A complex containing E2F, RB, and c-Abl is detected in vivo and can be assembled in vitro. We propose that the biological activity of RB not only depends on the inhibition of its targets but also on its ability to properly assemble specific protein complexes. Consistent with this hypothesis, a fragment of RB, SE delta, containing only the C pocket is shown to act as a dominant-negative inhibitor of RB function. SE delta does not have growth inhibitory activity of its own. When coexpressed with full-length RB, SE delta does not disrupt the RB-E2F or RB-D2 complexes nor does it affect the expression, phosphorylation, or nuclear tethering of the full-length RB. SE delta does compete with RB for binding to c-Abl and is fully capable of inhibiting the c-Abl tyrosine kinase. Thus, SE delta can inactivate RB while maintaining the inhibition of E2F and c-Abl. These results suggest that the inhibition of RB-binding proteins is not sufficient to suppress cell growth and that the assembly of RB-mediated protein complexes is also important for the promotion of cell-cycle arrest.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Welch PJ,Wang JYdoi
10.1101/gad.9.1.31subject
Has Abstractpub_date
1995-01-01 00:00:00pages
31-46issue
1eissn
0890-9369issn
1549-5477journal_volume
9pub_type
杂志文章abstract：:Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.455908
更新日期：2008-02-01 00:00:00
abstract：:Chromosome replication occurs precisely once during the cell cycle of almost all eukaryotic cells, and is a highly complex process that is still understood relatively poorly. Two conserved kinases called Cdc7 (cell division cycle 7) and cyclin-dependent kinase (CDK) are required to establish replication forks during t...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.1933010
更新日期：2010-06-15 00:00:00
abstract：:Classical embryology has provided a clear view of the timing and hormonal cues that govern sexual differentiation. Molecular biology has added important details to this picture. The cloning of SRY, MIS, and INSL3 provide insight into the molecular signals that provide important cues at the cellular level. Continued un...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.843800
更新日期：2000-12-15 00:00:00
abstract：:The bHLH-PAS transcription factor SIM1 is expressed during the development of the hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.20.3264
更新日期：1998-10-15 00:00:00
abstract：:All viruses require cellular ribosomes to translate their mRNAs. Viruses producing methyl-7 (m⁷) GTP-capped mRNAs, like Herpes Simplex Virus-1 (HSV-1), stimulate cap-dependent translation by activating mTORC1 to inhibit the translational repressor 4E-binding protein 1 (4E-BP1). Here, we establish that the HSV-1 kinase...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1978310
更新日期：2010-12-01 00:00:00
abstract：:Using an in vitro system in which a 5' splice site (5'SS) RNA oligo (AAG decreases GUAAGUAdT) is capable of inducing formation of U2/U4/U5/U6 snRNP complex we show that this oligo specifically binds to U4/U5/U6 snRNP and cross-links to U6 snRNA in the absence of U2 snRNP. Moreover, 5'SS RNA oligo bound to U4/U5/U6 snR...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.16.1962
更新日期：1994-08-15 00:00:00
abstract：:The Agrobacterium Ti plasmid (T-DNA) 6b proteins interact with many different host proteins implicated in plant cell proliferation. Here, we show that Arabidopsis plants overexpressing 6b display microRNA (miRNA) deficiency by directly targeting SERRATE and AGO1 via a specific loop fragment (residues 40-55). In additi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1985511
更新日期：2011-01-01 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
abstract：:Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF) family is composed of complexes that contain either Brg1 or hBrm as the central ATPase; however, these separate complexes have not been compared functionally. Here...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.872801
更新日期：2001-03-01 00:00:00
abstract：:A relevant, yet little recognized feature of antisense regulation is the possibility of switching roles between regulatory and regulated RNAs. Here we show that induction of a Salmonella gene relies on the conversion of a small RNA from effector to regulatory target. The chiP gene (formerly ybfM), identified and chara...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.541609
更新日期：2009-09-01 00:00:00
abstract：:In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.179663.111
更新日期：2012-01-15 00:00:00
abstract：:We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ri...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.8.1023
更新日期：1997-04-15 00:00:00
abstract：:The genes pannier (pnr) and u-shaped (ush) are required for the regulation of achaete-scute during establishment of the bristle pattern in Drosophila. pnr encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein. Genetic interactions between dominant pnr ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.22.3096
更新日期：1997-11-15 00:00:00
abstract：:Activation and repression of transcription in eukaryotes involve changes in the chromatin fiber that can be accomplished by covalent modification of the histone tails or the replacement of the canonical histones with other variants. Here we show that the histone H2A variant of Drosophila melanogaster, H2Av, localizes ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1259105
更新日期：2005-01-01 00:00:00
abstract：:The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping fact...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.227843.113
更新日期：2013-12-15 00:00:00
abstract：:Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing individual effector domains, the role of paired domains and how they functi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.220467.113
更新日期：2013-06-01 00:00:00
abstract：:The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evid...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.292318.116
更新日期：2017-03-15 00:00:00
abstract：:The X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals. Over recent years an important goal has been to understand how Xist is regulated at the initiation of X inactivation. Here we report the analysis of a series of targeted mutations at the 5' end o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.271203
更新日期：2003-09-01 00:00:00
abstract：:Accurate and regulated transcription by RNA polymerase II requires the assembly of an initiation complex involving multiple protein-DNA and protein-protein interactions. A key event is binding of TFIID, a complex consisting of TBP and associated factors (TAFs) to the template DNA. The TAF subunits of TFIID carry out d...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.22.2747
更新日期：1995-11-15 00:00:00
abstract：:Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.6.1120
更新日期：1992-06-01 00:00:00
abstract：:Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap-dep...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.889201
更新日期：2001-08-15 00:00:00
abstract：:Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.5.640
更新日期：1998-03-01 00:00:00
abstract：:Asymmetric localization of cell fate determinants is a crucial step in neuroblast asymmetric divisions. Whereas several protein kinases have been shown to mediate this process, no protein phosphatase has so far been implicated. In a clonal screen of larval neuroblasts we identified the evolutionarily conserved Protein...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1723609
更新日期：2009-02-01 00:00:00
abstract：:The efficiency of RNA 3'-end formation of spleen necrosis virus (SNV) is determined by the distance between the cap site and the poly(A) site. When the distance between the cap site and the poly(A) site was shorter than 500 bases, only 3-9% of the RNA was polyadenylated at the SNV poly(A) site. However, when the dista...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.12b.2299
更新日期：1990-12-01 00:00:00
abstract：:Alternative pre-mRNA splicing determines many changes in gene expression during development. Two regulators known to control splicing patterns during neuron and muscle differentiation are the polypyrimidine tract-binding protein (PTB) and its neuronal homolog nPTB. These proteins repress certain exons in early myoblas...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1500707
更新日期：2007-01-01 00:00:00
abstract：:Early endoderm formation in zebrafish requires at least three loci that function downstream of Nodal signaling but upstream of the early endodermal marker sox17: bonnie and clyde (bon), faust (fau), and casanova (cas). cas mutants show the most severe phenotype as they do not form any gut tissue and lack all sox17 exp...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.892301
更新日期：2001-06-15 00:00:00
abstract：:Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profili...
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
abstract：:RNAi has revolutionized reverse genetics; however, RNAi is not necessarily ubiquitous or constitutive. Lund and colleagues (pp. 1121-1131) show that microRNA (miRNA) effector Argonautes (Agos) are limiting and easily saturated during early Xenopus embryogenesis. Moreover, this stage is devoid of slicing capacity. Supp...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.2062911
更新日期：2011-06-01 00:00:00
abstract：:To investigate the relationship between splicing and polyadenylation during the production of vertebrate mRNAs, we examined the effect of mutation of a poly(A) site on splicing of upstream introns. Mutation of the AAUAAA polyadenylation consensus sequence inhibited in vitro splicing of an upstream intron. The magnitud...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.11.2086
更新日期：1991-11-01 00:00:00
abstract：:Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LI...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.181933.111
更新日期：2012-03-01 00:00:00
