Abstract:
:In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of cells with an exogenous source of cholesterol. Fibroblasts from patients with the heterozygous form of familial hypercholesterolemia (FH) possess one functional allele and one nonfunctional allele at the LDL receptor locus. In the current studies, we have examined the effect that this deficiency produces upon the pattern of regulation of the single functional allele at the LDL receptor locus. Under growth conditions that induced a maximal rate of LDL receptor synthesis (that is, growth in the absence of an exogenous source of cholesterol), the FH heterozygote cells produced about one half as many functional LDL receptors as did the normal cells. More importantly, when grown in the presence of increasing amounts of exogenous cholesterol, the FH heterozygote and normal cells suppressed their respective LDL receptor activities in parallel. Over a wide range of LDL receptor activities, at each level of cellular esterified cholesterol, the FH heterozygote cells expressed about one half as many receptors as did the normal cells. These data indicate that in the FH heterozygote cells, the receptor regulatory mechanism dictates that the normal allele produce only the amount of gene product that it would normally produce at a given level of cellular esterified cholesterol. The failure of the regulatory mechanism to stimulate the normal allele at the LDL receptor locus to produce twice its normal amount of gene product leaves the FH heterozygote cells with a persistent 50% deficiency in LDL receptors under all conditions of cell growth.
journal_name
Celljournal_title
Cellauthors
Goldstein JL,Sobhani MK,Faust JR,Brown MSdoi
10.1016/0092-8674(76)90110-0subject
Has Abstractpub_date
1976-10-01 00:00:00pages
195-203issue
2eissn
0092-8674issn
1097-4172pii
0092-8674(76)90110-0journal_volume
9pub_type
杂志文章相关文献
CELL文献大全abstract::The assembly of new histones into nucleosomes and the segregation of old histones during replication were investigated using a density gradient, sedimentation equilibrium analysis of histones labeled in vivo with dense amino acids. After a 1 hr pulse of dense amino acids and 3H-lysine, nucleosomes were isolated from c...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(77)90282-3
更新日期:1977-11-01 00:00:00
abstract::Social isolation is a stressful condition that often leads to maladaptive behaviors. In this issue of Cell, Zelikowsky et al. find that chronic social isolation stress triggers an increase in neuronal tachykinin signaling across distinct brain regions that mediate fear and aggression, elucidating the neural basis of t...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2018.04.031
更新日期:2018-05-17 00:00:00
abstract::An attenuated form of familial adenomatous polyposis coli, AAPC, causes relatively few colonic polyps, but still carries a significant risk of colon cancer. The mutant alleles responsible for this attenuated phenotype have been mapped in several families to the adenomatous polyposis coli (APC) locus on human chromosom...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90538-2
更新日期:1993-12-03 00:00:00
abstract::Signaling by TGF beta-related factors requires ligand-induced association between type I and type II transmembrane serine/threonine kinases. In Drosophila, the saxophone (sax) and thick veins (tkv) genes encode type I receptors that mediate signaling by decapentaplegic (dpp), a member of the bone morphogenetic protein...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90293-7
更新日期:1995-03-24 00:00:00
abstract::Homologous recombination in embryonal stem cells has been used to produce a fusion oncogene, thereby mimicking chromosomal translocations that frequently result in formation of tumor-specific fusion oncogenes in human malignancies. AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81269-6
更新日期:1996-06-14 00:00:00
abstract::Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase l...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.05.036
更新日期:2017-06-15 00:00:00
abstract::Recent work has identified a cascade of membrane bound protein kinases in Ehrlich ascites tumor cells. These enzymes, designated PKL, PKS and PKM, are present in both Ehrlich tumor and mouse brain, but the cascade is active only in the tumor tissue. We have now purified a fourth protein kinase, PKF, that is also assoc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90227-0
更新日期:1981-07-01 00:00:00
abstract::Phosphoinositide 3 kinase (PI3K) is a key signaling enzyme implicated in receptor-stimulated mitogenesis, oxidative bursting in neutrophils, membrane ruffling, and glucose uptake. A PI3K has already been purified, cloned, and shown to be regulated by receptors that act via tyrosine kinase-dependent regulatory mechanis...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90237-2
更新日期:1994-04-08 00:00:00
abstract::Bacterial gene expression depends not only on specific regulatory mechanisms, but also on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding of these global effects is necessary for a quantitative understanding of ge...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.12.001
更新日期:2009-12-24 00:00:00
abstract::The transcription factor HIF-1 mediates adaptive responses to hypoxia, and its activity is negatively regulated by O2-dependent binding of the von Hippel-Lindau (VHL) protein. In this issue, Boutin et al. (2008) use conditional knockout mice to demonstrate that sensing of O2 by keratinocytes in the epidermis leads to ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2008.04.004
更新日期:2008-04-18 00:00:00
abstract::Micronuclei of Tetrahymena thermophila contain two electrophoretically distinct forms of histone H3. The slower migrating micronuclear species, H3S, is indistinguishable from the macronuclear H3 by electrophoretic analyses in three gel systems and by partial proteolytic peptide mapping. The faster species, H3F, is uni...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90234-2
更新日期:1980-05-01 00:00:00
abstract::The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2012.07.032
更新日期:2012-09-14 00:00:00
abstract::Neurons in the cerebral cortex connect through descending pathways to hindbrain and spinal cord to activate muscle and generate movement. Although components of this pathway have been previously generated and studied in vitro, the assembly of this multi-synaptic circuit has not yet been achieved with human cells. Here...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.11.017
更新日期:2020-12-23 00:00:00
abstract::Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.10.026
更新日期:2015-11-05 00:00:00
abstract::NPR1 is an essential regulator of plant systemic acquired resistance (SAR), which confers immunity to a broad-spectrum of pathogens. SAR induction results in accumulation of the signal molecule salicylic acid (SA), which induces defense gene expression via activation of NPR1. We found that in an uninduced state, NPR1 ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00429-x
更新日期:2003-06-27 00:00:00
abstract::Using cryo-electron microscopy, we have solved the structure of an icosidodecahedral COPII coat involved in cargo export from the endoplasmic reticulum (ER) coassembled from purified cargo adaptor Sec23-24 and Sec13-31 lattice-forming complexes. The coat structure shows a tetrameric assembly of the Sec23-24 adaptor la...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.06.024
更新日期:2008-08-08 00:00:00
abstract::Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00241-1
更新日期:2003-04-18 00:00:00
abstract::Tumor suppressors block the development of cancer and are often lost during tumor development. Papa et al. show that partial loss of normal PTEN tumor suppressor function can be compounded by additional disruption caused by the expression of inactive mutant PTEN protein. This has significant implications for patients ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2014.04.008
更新日期:2014-04-24 00:00:00
abstract::Nutrition presents unanswered scientific questions of high public health importance. We envision model systems composed of interacting gastrointestinal and metabolic tissues derived from human embryonic stem cells, populated by gut microbiota. The culture will be embedded in 3D scaffolds, creating a controlled experim...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.02.039
更新日期:2015-03-26 00:00:00
abstract::Human autoantibodies that recognize the spindle poles of mammals, plants, and insects were found to recognize two antigens in yeast. One of these proteins, called SPA1 (for Spindle Pole Antigen), is antigenically related to the spindle poles of a diverse set of organisms. The gene encoding SPA1 was cloned by immunoscr...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(88)90977-4
更新日期:1988-09-09 00:00:00
abstract::Methylation of arginine residues within histone H3 has been linked to active transcription. This modification appears on the estrogen-regulated pS2 promoter when the CARM1 methyltransferase is recruited during transcriptional activation. Here we describe a process, deimination, that converts histone arginine to citrul...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2004.08.020
更新日期:2004-09-03 00:00:00
abstract::Plasma membrane vesicles and protoplasts of Escherichia coli were fused to planar lipid bilayers and studied with electrophysiological techniques. Large transmembrane aqueous channels were opened when 0.2 nM LamB signal peptide was added to the cytoplasmic side of the membrane. These aqueous pores are similar in condu...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90231-z
更新日期:1992-05-15 00:00:00
abstract::Signaling by the epidermal growth factor receptor requires an allosteric interaction between the kinase domains of two receptors, whereby one activates the other. We show that the intracellular juxtamembrane segment of the receptor, known to potentiate kinase activity, is able to dimerize the kinase domains. The C-ter...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.04.025
更新日期:2009-06-26 00:00:00
abstract::The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with either short or long 3' untranslated regions (3' UTRs). The physiological significance of the two forms of mRNAs encoding the same protein is unknown. Here, we show that the short and long 3' UTR BDNF mRNAs are involved in different cell...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.05.045
更新日期:2008-07-11 00:00:00
abstract::Heat shock and other proteotoxic stresses cause accumulation of nonnative proteins that trigger activation of heat shock protein (Hsp) genes. A chaperone/Hsp functioning as repressor of heat shock transcription factor (HSF) could make activation of hsp genes dependent on protein unfolding. In a novel in vitro system, ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81588-3
更新日期:1998-08-21 00:00:00
abstract::The fasciclin I, II, and III glycoproteins are expressed on different subsets of axon bundles (fascicles) in insect embryos and are thus candidates for surface recognition molecules involved in growth cone guidance. Here we present the sequence of grasshopper fasciclin I and the identification and sequence of the Dros...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90574-0
更新日期:1988-05-20 00:00:00
abstract::DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks conver...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.08.030
更新日期:2008-09-19 00:00:00
abstract::Csm, a type III-A CRISPR-Cas interference complex, is a CRISPR RNA (crRNA)-guided RNase that also possesses target RNA-dependent DNase and cyclic oligoadenylate (cOA) synthetase activities. However, the structural features allowing target RNA-binding-dependent activation of DNA cleavage and cOA generation remain unkno...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.10.052
更新日期:2019-01-10 00:00:00
abstract::Recent results from diverse organisms point to a self-reinforcing network of interactions among the three best-characterized covalent modifications that mark heterochromatin: histone hypoacetylation, histone H3-Lys9 methylation, and cytosine methylation. These modification systems suggest a mechanistic basis for sprea...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/s0092-8674(02)00644-x
更新日期:2002-02-22 00:00:00
abstract::The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2006.05.041
更新日期:2006-07-28 00:00:00