Abstract:
:The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by codepletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of the cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive X (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S-phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Sun X,Bizhanova A,Matheson TD,Yu J,Zhu LJ,Kaufman PDdoi
10.1128/MCB.00569-16subject
Has Abstractpub_date
2017-08-11 00:00:00issue
17eissn
0270-7306issn
1098-5549pii
MCB.00569-16journal_volume
37pub_type
杂志文章abstract::The Moloney murine sarcoma virus long terminal repeat (LTR) harbors two distinct positive activators of transcription, namely, a distal signal and an enhancer. In this report we demonstrate that infection by herpes simplex virus (HSV) can markedly affect the utilization of these two Moloney murine sarcoma virus transc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.8.1959
更新日期:1985-08-01 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::Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of T...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01437-09
更新日期:2010-04-01 00:00:00
abstract::Chromatin is regulated by cross talk among different histone modifications, which can occur between residues within the same tail or different tails in the nucleosome. The latter is referred to as trans-tail regulation, and the best-characterized example of this is the dependence of H3 methylation on H2B ubiquitylatio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00324-10
更新日期:2010-07-01 00:00:00
abstract::Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative fun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5041-5049.2001
更新日期:2001-08-01 00:00:00
abstract::We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more dis...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.911
更新日期:1993-02-01 00:00:00
abstract::We analyzed the binding site(s) for Grb2 on the epidermal growth factor (EGF) receptor (EGFR), using cell lines overexpressing EGFRs containing various point and deletion mutations in the carboxy-terminal tail. Results of co-immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173 mediate the bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5192
更新日期:1994-08-01 00:00:00
abstract::Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-der...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00385-13
更新日期:2013-10-01 00:00:00
abstract::To study the relationship between oncogenesis by v-src and normal cellular signalling pathways, we determined the effects of v-src on 3T3-TNR9 cells, a Swiss 3T3 variant which does not respond mitogenically to tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We found that src was unable to transfor...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.8.4155
更新日期:1990-08-01 00:00:00
abstract::The PKC1-associated mitogen-activated protein (MAP) kinase pathway of Saccharomyces cerevisiae regulates cell integrity by controlling the actin cytoskeleton and cell wall synthesis. Activation of PKC1 occurs via the GTPase RHO1 and the kinase pair PKH1 and PKH2. Here we report that YPK1 and YPK2, an essential pair of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.5.1329-1339.2002
更新日期:2002-03-01 00:00:00
abstract::Elastin, an extracellular component of arteries, lung, and skin, is produced during fetal and neonatal growth. We reported previously that the cessation of elastin production is controlled by a posttranscriptional mechanism. Although tropoelastin pre-mRNA is transcribed at the same rate in neonates and adults, marked ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.11.7314
更新日期:1999-11-01 00:00:00
abstract::Mutations in mitochondrial DNA (mtDNA) cause a variety of relatively rare human diseases and may contribute to the pathogenesis of other, more common degenerative diseases. This stimulates interest in the capacity of mitochondria to repair damage to mtDNA. Several recent studies have shown that some types of damage to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.3.1257
更新日期:1998-03-01 00:00:00
abstract::SEC62 is required for the import of secretory protein precursors into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae. The DNA sequence of SEC62 predicts a 32-kDa polypeptide with two potential membrane-spanning segments. Two antisera directed against different portions of the SEC62 coding region specifical...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.11.6024
更新日期:1990-11-01 00:00:00
abstract::Minichromosome maintenance protein 1 (Mcm1) is required for efficient replication of autonomously replicating sequence (ARS)-containing plasmids in yeast cells. Reduced DNA binding activity in the Mcm1-1 mutant protein (P97L) results in selective initiation of a subset of replication origins and causes instability of ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.14.6514-6524.2004
更新日期:2004-07-01 00:00:00
abstract::Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00908-07
更新日期:2007-11-01 00:00:00
abstract::Correct reprogramming of epigenetic marks in the donor nuclei is crucial for successful cloning by nuclear transfer. Specific epigenetic modifications, such as repressive histone lysine methylation marks, are known to be very stable and difficult to reprogram. The discovery of histone lysine demethylases has opened up...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01014-12
更新日期:2013-03-01 00:00:00
abstract::Expression of the avian very-low-density apolipoprotein II (apoVLDLII) gene is completely dependent on estrogen and restricted to the liver. We have identified binding sites for nonhistone nuclear proteins located between -1.96 and -2.61 kilobases. One of these sites, located at -2.6 kilobases (designated site 1), was...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.1.154
更新日期:1990-01-01 00:00:00
abstract::Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype. By using a differential hybridization screen, an opaque-specific cDNA, Op1a, which represents the transcript of a gene regulated by switching, has been isolate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.2997
更新日期:1992-07-01 00:00:00
abstract::Rad23 and Rpn10 play synergistic roles in the recognition of ubiquitinated proteins by the proteasome, and loss of both proteins causes growth and proteolytic defects. However, the physiological targets of Rad23 and Rpn10 have not been well defined. We report that rad23Delta rpn10Delta is unable to grow in the presenc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.1.403-413.2005
更新日期:2005-01-01 00:00:00
abstract::Many selectable mutants of somatic Chinese hamster cells have been described, but very few of the mutations have been mapped to specific chromosomes. We have utilized the microcell-mediated gene transfer technique to establish the location of three selectable genetic markers on chromosome 2 of Chinese hamster. Microce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.4.330
更新日期:1981-04-01 00:00:00
abstract::Selective and accurate transcription of purified genes by RNA polymerase II requires multiple factors. The factor designated TFIID was purified extensively from HeLa cell nuclear extracts by using a simple and novel complementation assay. Thus, TFIID was preferentially inactivated by mild heat treatment of a nuclear e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.10.4028
更新日期:1988-10-01 00:00:00
abstract::The autonomously replicating rRNA genes (rDNA) in the somatic nucleus of Tetrahymena thermophila are maintained at a copy number of approximately 10(4) per nucleus. A mutant in which the replication properties of this molecule were altered was isolated and characterized. This mutation of inbred strain C3, named rmm4, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.2.452
更新日期:1989-02-01 00:00:00
abstract::The expression of the c-jun proto-oncogene is rapidly induced in response to mitogens acting on a large variety of cell surface receptors. The resulting functional activity of c-Jun proteins appears to be critical for cell proliferation. Recently, we have shown that a large family of G protein-coupled receptors (GPCRs...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.4289
更新日期:1999-06-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene CDC1 cause defects in Golgi inheritance and actin polarization. However, the biochemical function of Cdc1p is unknown. Previous work showed that cdc1 mutants accumulate intracellular Ca(2+) and display enhanced sensitivity to the extracellu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00567-07
更新日期:2008-05-01 00:00:00
abstract::ABFI (ARS-binding protein I) is a yeast protein that binds specific DNA sequences associated with several autonomously replicating sequences (ARSs). ABFI also binds sequences located in promoter regions of some yeast genes, including DED1, an essential gene of unknown function that is transcribed constitutively at a h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.887
更新日期:1990-03-01 00:00:00
abstract::CD146, an endothelial biomarker, has been shown to be aberrantly upregulated during pathological angiogenesis and functions as a coreceptor for vascular endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression. However, the regulatory mechanisms of CD146 expression during angiogenesis remain uncle...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00343-13
更新日期:2013-09-01 00:00:00
abstract::Malignant gliomas are highly lethal neoplasms with limited treatment options. We previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is universally and highly expressed in human gliomas. In this study, we investigated the biological activity of GPC1 expression in both human glioma cells and normal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,收录出版
doi:10.1128/MCB.00238-13
更新日期:2013-11-01 00:00:00
abstract::The family of p21-activated protein kinases (PAKs) appear to be present in all organisms that have Cdc42-like GTPases. In mammalian cells, PAKs have been implicated in the activation of mitogen-activated protein kinase cascades, but there are no reported effects of these kinases on the cytoskeleton. Recently we have s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.3.1129
更新日期:1997-03-01 00:00:00
abstract::ARGRI, ARGRII, and ARGRIII proteins regulate the expression of arginine anabolic and catabolic genes. The integrity of these three proteins is required to observe the formation of a DNA-protein complex with the different promoters of arginine coregulated genes. A study of deletions and point mutations created in the 5...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.5.2852
更新日期:1991-05-01 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