Abstract：
:Oscillations in cyclin-dependent kinase (CDK) activity drive the somatic cell cycle. After entry into mitosis, CDKs activate the anaphase-promoting complex (APC), which then promotes cyclin degradation and mitotic exit. The re-accumulation of cyclin A causes the inactivation of APC and entry into S phase, but how cyclin A can accumulate in the presence of active APC has remained unclear. Here we show that, during G1, APC autonomously switches to a state permissive for cyclin A accumulation. Crucial to this transition is the APC(Cdh1)-dependent autoubiquitination and proteasomal degradation of the ubiquitin-conjugating enzyme (E2) UbcH10. Because APC substrates inhibit the autoubiquitination of UbcH10, but not its E2 function, APC activity is maintained as long as G1 substrates are present. Thus, through UbcH10 degradation and cyclin A stabilization, APC autonomously downregulates its activity. This indicates that the core of the metazoan cell cycle could be described as a self-perpetuating but highly regulated oscillator composed of alternating CDK and APC activities.
journal_name
Naturejournal_title
Natureauthors
Rape M,Kirschner MWdoi
10.1038/nature03023keywords:
subject
Has Abstractpub_date
2004-12-02 00:00:00pages
588-95issue
7017eissn
0028-0836issn
1476-4687pii
nature03023journal_volume
432pub_type
杂志文章相关文献
NATURE文献大全abstract：:Amino-acid radicals play key roles in many enzymatic reactions. Catalysis often involves transfer of a radical character within the protein, as in class I ribonucleotide reductase where radical transfer occurs over 35 A, from a tyrosyl radical to a cysteine. It is currently debated whether this kind of long-range tran...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35014644
更新日期：2000-06-01 00:00:00
abstract：:Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calci...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature25511
更新日期：2018-03-29 00:00:00
abstract：:As an approach to the study of the kind of chemical process that might have contributed to the origin of life, attempts have been made to develop purely chemical systems in which oligonucleotides self-replicate. Although performed oligonucleotides have been shown to facilitate the formation of their complements from a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/327346a0
更新日期：1987-05-28 00:00:00
abstract：:Osteoclasts are the only somatic cells with bone-resorbing capacity and, as such, they have a critical role not only in normal bone homeostasis (called 'bone remodelling') but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis. A major focus of research in the field ha...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07713
更新日期：2009-03-26 00:00:00
abstract：:The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature21705
更新日期：2017-03-16 00:00:00
abstract：:Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait. Here we map the MEN-1 locus to chromosome 11 by family studies, and demonstrate ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/332085a0
更新日期：1988-03-03 00:00:00
abstract：:High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly during their propagation, provide a probe of Galactic high-energy processes and may enable the observation of phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been measured directly up to approximately 2 ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature24475
更新日期：2017-12-07 00:00:00
abstract：:Proteolysis is essential for the execution of many cellular functions. These include removal of incorrectly folded or damaged proteins, the activation of transcription factors, the ordered degradation of proteins involved in cell cycle control, and the generation of peptides destined for presentation by class I molecu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/33443
更新日期：1998-04-09 00:00:00
abstract：:All living organisms use ion channels to regulate the transport of ions across cellular membranes. Certain ion channels are classed as voltage-dependent because they have a voltage-sensing structure that induces their pores to open in response to changes in the cell membrane voltage. Until recently, the voltage-depend...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01473
更新日期：2003-03-13 00:00:00
abstract：:The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive imm...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature15254
更新日期：2015-10-01 00:00:00
abstract：:The central nervous system (CNS) requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for neural function. This environment is maintained by the 'blood-brain barrier' (BBB), which is composed of blood vessels whose endothelial cells display specialized tight...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13324
更新日期：2014-05-22 00:00:00
abstract：:Criteria for 'green buildings' need to make energy performance a priority--as do universities. ...
journal_title：Nature
pub_type： 社论
doi：10.1038/461146a
更新日期：2009-09-10 00:00:00
abstract：:As the extracellular matrix at the original site of a neuromuscular junction seems to play a major part in the specificity of synaptic regeneration, considerable attention has been paid to unique molecules localized to this region. Here we describe an extracellular matrix glycoprotein of the elasmobranch electric orga...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/314441a0
更新日期：1985-04-04 00:00:00
abstract：:A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/258677a0
更新日期：1975-12-25 00:00:00
abstract：:A biologically active complementary DNA clone of a transforming gene present in a human colon carcinoma contains gene sequences of both tropomyosin and a previously unknown protein tyrosine kinase. The predicted protein (641 amino acids) encoded by this oncogene seems to have been formed by a somatic rearrangement tha...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/319743a0
更新日期：1986-02-27 00:00:00
abstract：:The actin cytoskeleton is regulated by GTP-hydrolysing proteins, the Rho GTPases, which act as molecular switches in diverse signal-transduction processes. Various bacterial toxins can inactivate Rho GTPases by ADP-ribosylation or glucosylation. Previous research has identified Rho proteins as putative targets for Esc...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/42735
更新日期：1997-06-12 00:00:00
abstract：:Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nucle...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1155-x
更新日期：2019-05-01 00:00:00
abstract：:The age of dense interstellar cloud cores, where stars and planets form, is a crucial parameter in star formation and difficult to measure. Some models predict rapid collapse, whereas others predict timescales of more than one million years (ref. 3). One possible approach to determining the age is through chemical cha...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13924
更新日期：2014-12-11 00:00:00
abstract：:Nitrogen is an essential nutrient for all organisms that must have been available since the origin of life. Abiotic processes including hydrothermal reduction, photochemical reactions, or lightning discharge could have converted atmospheric N2 into assimilable NH4(+), HCN, or NOx species, collectively termed fixed nit...
journal_title：Nature
pub_type： 历史文章,杂志文章
doi：10.1038/nature14180
更新日期：2015-04-30 00:00:00
abstract：:Mitogen-activated protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors. In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/369418a0
更新日期：1994-06-02 00:00:00
abstract：:Microbes comprise the majority of extant organisms, yet much remains to be learned about the nature and driving forces of microbial diversification. Our understanding of how microorganisms adapt and evolve can be advanced by genome-wide documentation of the patterns of genetic exchange, particularly if analyses target...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05624
更新日期：2007-03-29 00:00:00
abstract：:Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of h...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10369
更新日期：2011-09-18 00:00:00
abstract：:Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins med...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature04443
更新日期：2006-02-09 00:00:00
abstract：:Since the discovery of insulin nearly 70 years ago, there has been no problem more fundamental to diabetes research than understanding how insulin works at the cellular level. Insulin binds to the alpha subunit of the insulin receptor which activates the tyrosine kinase in the beta subunit, but the molecular events li...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/352073a0
更新日期：1991-07-04 00:00:00
abstract：:Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods. Nature uses sophisticated templates such as the ribosome, whereas chemists use simple ions or small molecules. But as we tackle the synthesis...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09683
更新日期：2011-01-06 00:00:00
abstract：:Distance determination in animals can be achieved by visual or non-visual cues. Weakly electric fish use active electrolocation for orientation in the dark. By perceiving self-produced electric signals with epidermal electroreceptors, fish can detect, locate and analyse nearby objects. Distance discrimination, however...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/27655
更新日期：1998-10-29 00:00:00
abstract：:The growth cycle in nutrient-rich, aquatic environments starts with a diatom bloom that ends in mass sinking of ungrazed cells and phytodetritus. The low grazing pressure on these blooms has been attributed to the inability of overwintering copepod populations to track them temporally. We tested an alternative explana...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02526
更新日期：2004-05-27 00:00:00
abstract：:The presence of large Northern Hemisphere ice sheets and reduced greenhouse gas concentrations during the Last Glacial Maximum fundamentally altered global ocean-atmosphere climate dynamics. Model simulations and palaeoclimate records suggest that glacial boundary conditions affected the El Niño-Southern Oscillation, ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature24669
更新日期：2018-02-15 00:00:00
abstract：:Keratinocytes of three different epithelia grown in cell culture express a large number of differentiation markers with either no differences or relatively small differences, depending on the species. Much of the distinctive phenotype of these epithelia in vivo must be due to external modulation and relatively little,...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/269489a0
更新日期：1977-10-06 00:00:00
abstract：:The additional author support information was erroneously omitted from the Supplementary Information. This has been corrected online. ...
journal_title：Nature
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41586-019-0959-z
更新日期：2019-02-01 00:00:00
