Abstract:
:Members of the type II nuclear hormone receptor subfamily (e.g., thyroid hormone receptors [TRs], retinoic acid receptors, retinoid X receptors [RXRs], vitamin D receptor, and the peroxisome proliferator-activated receptors) bind to their response sequences with or without ligand. In the absence of ligand, these DNA-bound receptors mediate different degrees of repression or silencing of gene expression which is thought to result from the association of their ligand binding domains (LBDs) with corepressors. Two related corepressors, N-CoR and SMRT, interact to various degrees with the LBDs of these type II receptors in the absence of their cognate ligands. N-CoR and SMRT have been proposed to act by recruiting class I histone deacetylases (HDAC I) through an association with Sin3, although they have also been shown to recruit class II HDACs through a Sin3-independent mechanism. In this study, we used a biochemical approach to identify novel nuclear factors that interact with unliganded full-length TR and RXR. We found that the DNA binding domains (DBDs) of TR and RXR associate with two proteins which we identified as PSF (polypyrimidine tract-binding protein-associated splicing factor) and NonO/p54(nrb). Our studies indicate that PSF is a novel repressor which interacts with Sin3A and mediates silencing through the recruitment of HDACs to the receptor DBD. In vivo studies with TR showed that although N-CoR fully dissociates in the presence of ligand, the levels of TR-bound PSF and Sin3A appear to remain unchanged, indicating that Sin3A can be recruited to the receptor independent of N-CoR or SMRT. RXR was not detected to bind N-CoR although it bound PSF and Sin3A as effectively as TR, and this association with RXR did not change with ligand. Our studies point to a novel PSF/Sin3-mediated pathway for nuclear hormone receptors, and possibly other transcription factors, which may fine-tune the transcriptional response as well as play an important role in mediating the repressive effects of those type II receptors which only weakly interact with N-CoR and SMRT.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Mathur M,Tucker PW,Samuels HHdoi
10.1128/MCB.21.7.2298-2311.2001subject
Has Abstractpub_date
2001-04-01 00:00:00pages
2298-311issue
7eissn
0270-7306issn
1098-5549journal_volume
21pub_type
杂志文章abstract::The UvsW protein of bacteriophage T4 is involved in many aspects of phage DNA metabolism, including repair, recombination, and recombination-dependent replication. UvsW has also been implicated in the repression of origin-dependent replication at late times of infection, when UvsW is normally synthesized. Two well-cha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.8.2706-2715.2001
更新日期:2001-04-01 00:00:00
abstract::Unique single-stranded regions of simian virus 40 DNA, phage M13 virion DNA, and several homopolymers were used as templates for the synthesis of (p)ppRNA-DNA chains by CV-1 cell DNA primase-DNA polymerase alpha. Intact RNA primers, specifically labeled with an RNA capping enzyme, were typically 6 to 8 ribonucleotides...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1170
更新日期:1985-05-01 00:00:00
abstract::Inactivation of the TATA-binding protein-containing complex TFIIIB contributes to the mitotic repression of RNA polymerase III transcription, both in frogs and in humans (J. M. Gottesfeld, V. J. Wolf, T. Dang, D. J. Forbes, and P. Hartl, Science 263:81-84, 1994; R. J. White, T. M. Gottlieb, C. S. Downes, and S. P. Jac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.6653
更新日期:1995-12-01 00:00:00
abstract::Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53(-/-) and p21(-/-)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.6748-6757.2001
更新日期:2001-10-01 00:00:00
abstract::p300 and the closely related CREB binding protein (CBP) are transcriptional adaptors that are present in intracellular complexes with TATA binding protein (TBP) and bind to upstream activators including p53 and nuclear hormone receptors. They have intrinsic and associated histone acetyltransferase activity, suggesting...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.6.3596
更新日期:1998-06-01 00:00:00
abstract::Precursor RNA containing the adenovirus L3 polyadenylation site is assembled into a 50S complex upon incubation with HeLa nuclear extract at 30 degrees C. The cofactor and sequence requirements for 50S complex formation are similar to those of the in vitro polyadenylation reaction. Assembly of this complex requires AT...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.226
更新日期:1988-01-01 00:00:00
abstract::Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01475-14
更新日期:2015-05-01 00:00:00
abstract::Filopodia are dynamic structures found at the leading edges of most migrating cells. IRSp53 plays a role in filopodium dynamics by coupling actin elongation with membrane protrusion. IRSp53 is a Cdc42 effector protein that contains an N-terminal inverse-BAR (Bin-amphipysin-Rvs) domain (IRSp53/MIM homology domain [IMD]...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01574-08
更新日期:2010-02-01 00:00:00
abstract::The activation of Raf kinases by the small GTPase Ras requires two major sets of phosphorylations. One set lies within the activation loop, and the other lies within the N-terminal acidic region (N region). In the most abundant isoform of Raf, C-Raf, N-region phosphorylations occur on serine 338 (S338) and tyrosine 34...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00132-17
更新日期:2017-09-12 00:00:00
abstract::Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factor...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7509-7522.2001
更新日期:2001-11-01 00:00:00
abstract::The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00080-19
更新日期:2019-08-12 00:00:00
abstract::Tight control of apoptosis is required for proper development and maintenance of homeostasis in multicellular organisms. Cells can protect themselves from potentially lethal stimuli by expressing antiapoptotic factors, such as inhibitors of apoptosis, FLICE (caspase 8)-inhibitory proteins, and members of the Bcl2 fami...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.23.10425-10436.2004
更新日期:2004-12-01 00:00:00
abstract::Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5032-5040.2000
更新日期:2000-07-01 00:00:00
abstract::Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several reg...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.5.2790
更新日期:1997-05-01 00:00:00
abstract::Posttranslational modifications (PTMs) can alter many fundamental properties of a protein. One or combinations of them have been known to regulate the dynamics of many cellular pathways and consequently regulate all vital processes. Understandably, pathogens have evolved sophisticated strategies to subvert these mecha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00397-15
更新日期:2015-09-01 00:00:00
abstract::In in vitro splicing reactions, influenza virus NS1 mRNA was not detectably spliced, but nonetheless very efficiently formed ATP-dependent 55S complexes containing the U1, U2, U4, U5, and U6 small nuclear ribonucleoproteins (snRNPs) (C. H. Agris, M. E. Nemeroff, and R. M. Krug, Mol. Cell. Biol. 9:259-267, 1989). We de...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.3.962
更新日期:1992-03-01 00:00:00
abstract::MOT1 is an essential Saccharomyces cerevisiae protein and a member of the SNF2/SWI2 family of ATPases. MOT1 functions by removing TATA-binding protein (TBP) from DNA, and as a consequence, MOT1 can regulate transcription both in vitro and in vivo. Here we describe the in vivo and in vitro activities of MOT1 deletion a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4842
更新日期:1997-08-01 00:00:00
abstract::A recent analysis of gene expression in renal cell carcinoma cells led to the identification of mRNAs whose translation was dependent on the presence of the von Hippel-Lindau (VHL) tumor suppressor gene product, pVHL. Here, we investigate the finding that pVHL-expressing RCC cells (VHL(+)) exhibited elevated levels of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.20.7083-7095.2003
更新日期:2003-10-01 00:00:00
abstract::The coactivator complexes TRAP/SMCC and PC2 represent two forms of Mediator. To further understand the implications of the heterogeneity of the cellular Mediator populations for regulation of RNA polymerase II (Pol II) transcription, we used a combination of affinity and conventional chromatographic methods. Our analy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2117-2129.2005
更新日期:2005-03-01 00:00:00
abstract::The intergenic spacer region of the Xenopus laevis ribosomal DNA contains multiple elements which are either 60 or 81 base pairs long. Clusters of these elements have previously been shown to act as position- and distance-independent enhancers on an RNA polymerase I promoter when located in cis. By a combination of de...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.10.4282
更新日期:1988-10-01 00:00:00
abstract::We have studied leucine transport in several Chinese hamster-human hybrid cell lines obtained by fusion of a temperature-sensitive line of Chinese hamster ovary cells, ts025C1, and normal human leukocytes. A hybrid cell line exhibiting a twofold increase in L-leucine uptake over that in the parental cell line was foun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.3.475
更新日期:1984-03-01 00:00:00
abstract::Flk2/Flt3 is a recently identified receptor tyrosine kinase expressed in brain, placenta, testis, and primitive hematopoietic cells. The mitogenic signalling potential and biochemical properties of Flk2/Flt3 have been analyzed by using a chimeric receptor composed of the extracellular domain of the human colony-stimul...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6572
更新日期:1993-10-01 00:00:00
abstract::The transcription of meiosis-specific genes, as well as the initiation of meiosis, in the budding yeast Saccharomyces cerevisiae depends on IME1. IME1 encodes a transcriptional activator which lacks known DNA binding motifs. In this study we have determined the mode by which Ime1 specifically activates the transcripti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.5.2518
更新日期:1996-05-01 00:00:00
abstract::ZO-1, ZO-2, and ZO-3 are closely related MAGUK family proteins that localize at the cytoplasmic surface of tight junctions (TJs). ZO-1 and ZO-2 are expressed in both epithelia and endothelia, whereas ZO-3 is exclusively expressed in epithelia. In spite of intensive studies of these TJ MAGUKs, our knowledge of their fu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01811-05
更新日期:2006-12-01 00:00:00
abstract::Sequence blocks within the core region were swapped among RNA polymerase II promoters to explore effects on transcription in vitro. The pair of blocks flanking TATA strongly influenced general transcription, with an additional effect on promoter activation. These flanking elements induced a change in the ratio of acti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.10.3608-3615.2000
更新日期:2000-05-01 00:00:00
abstract::The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G(1) phase to S phase. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.21.9527-9541.2004
更新日期:2004-11-01 00:00:00
abstract::Glucose release from hepatocytes is important for maintenance of blood glucose levels. Glucose-6-phosphate phosphatase, catalyzing the final metabolic step of gluconeogenesis, faces the endoplasmic reticulum (ER) lumen. Thus, glucose produced in the ER has to be either exported from the ER into the cytosol before rele...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.24.11102-11112.2005
更新日期:2005-12-01 00:00:00
abstract::The Src homology 2-containing phosphotyrosine phosphatase (SHP2) is primarily a positive effector of receptor tyrosine kinase signaling. However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.21.7875-7886.2003
更新日期:2003-11-01 00:00:00
abstract::Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.12.5496-5509.2004
更新日期:2004-06-01 00:00:00
abstract::Xrn1p of Saccharomyces cerevisiae is a major cytoplasmic RNA turnover exonuclease which is evolutionarily conserved from yeasts to mammals. Deletion of the XRN1 gene causes pleiotropic phenotypes, which have been interpreted as indirect consequences of the RNA turnover defect. By sequence comparisons, we have identifi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.5930
更新日期:1999-09-01 00:00:00