Abstract:
:The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C.
journal_name
Cell Repjournal_title
Cell reportsauthors
Wild T,Larsen MS,Narita T,Schou J,Nilsson J,Choudhary Cdoi
10.1016/j.celrep.2016.01.060subject
Has Abstractpub_date
2016-03-01 00:00:00pages
1829-40issue
8issn
2211-1247pii
S2211-1247(16)30038-9journal_volume
14pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by "self-condensation" culture based on...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.123
更新日期:2018-05-08 00:00:00
abstract::Eukaryotic genomes are almost entirely transcribed by RNA polymerase II. Consequently, the transcription of long noncoding RNAs often overlaps with coding gene promoters, triggering potential gene repression through a poorly characterized mechanism of transcription interference. Here, we propose a comprehensive model ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107612
更新日期:2020-05-05 00:00:00
abstract::Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activit...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.10.077
更新日期:2016-11-22 00:00:00
abstract::Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid f...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.022
更新日期:2018-03-27 00:00:00
abstract::RIP1 is a central mediator of cell death in response to cell stress but can also mediate cell survival by activating NF-κB. Here, we show that RIP1 acts as a switch in EGFR signaling. EGFRvIII is an oncogenic mutant that does not bind ligand and is coexpressed with EGFRWT in glioblastoma multiforme (GBM). EGFRvIII rec...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.07.025
更新日期:2013-08-29 00:00:00
abstract::MicroRNAs (miRNAs) are typically generated as ~22-nucleotide double-stranded RNAs via the processing of precursor hairpins by the ribonuclease III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form an RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoiet...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.09.029
更新日期:2013-11-14 00:00:00
abstract::Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by thes...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.03.018
更新日期:2014-04-24 00:00:00
abstract::Megakaryocytes (MKs) come from a complex process of hematopoietic progenitor maturation within the bone marrow that gives rise to de novo circulating platelets. Bone marrow microenvironment contains a large number of adipocytes with a still ill-defined role. This study aims to analyze the influence of adipocytes and i...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107875
更新日期:2020-07-07 00:00:00
abstract::Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. He...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.104
更新日期:2016-08-16 00:00:00
abstract::The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compound...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.06.013
更新日期:2013-07-11 00:00:00
abstract::Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.03.005
更新日期:2017-03-28 00:00:00
abstract::Modeling late-onset disorders such as Parkinson's disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC mo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.062
更新日期:2016-10-18 00:00:00
abstract::Uveal melanoma (UM) is characterized by mutually exclusive activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4, four genes in a linear pathway to activation of PLCβ in almost all tumors and loss of BAP1 in the aggressive subset. We generated mice with melanocyte-specific expression of GNA11Q209L with and without h...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.01.081
更新日期:2018-02-27 00:00:00
abstract::CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the interplay of both cell types and their role in tumor suppression still remain elusive. In this study, we investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse mo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.10.086
更新日期:2016-11-22 00:00:00
abstract::In plants, the phytohormone auxin acts as a master regulator of developmental processes and environmental responses. The best characterized process in the auxin regulatory network occurs at the subcellular scale, wherein auxin mediates signal transduction into transcriptional programs by triggering the degradation of ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.074
更新日期:2018-03-13 00:00:00
abstract::Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.072
更新日期:2018-01-16 00:00:00
abstract::Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA d...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.02.040
更新日期:2017-03-07 00:00:00
abstract::Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.051
更新日期:2018-05-15 00:00:00
abstract::The Argonaute subfamily of proteins (AGO) loads microRNAs (miRNAs) to form the effector complex that mediates target gene silencing. Empty AGO, but not miRNA-loaded AGO, is selectively degraded across species. We have reported that the degradation of empty AGO is part of a quality control pathway that eliminates dysfu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.003
更新日期:2019-07-30 00:00:00
abstract::The achievement of the final form of an individual requires not only the control of cell size and differentiation but also integrative directional cues to instruct cell movements, positions, and orientations. In Drosophila, the adult epidermis of the abdomen is created de novo by histoblasts. As these expand and fuse,...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.036
更新日期:2018-12-04 00:00:00
abstract::CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient exp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.05.061
更新日期:2019-06-18 00:00:00
abstract::Desensitization, signaling, and trafficking of G-protein-coupled receptors (GPCRs) are critically regulated by multifunctional adaptor proteins, β-arrestins (βarrs). The two isoforms of βarrs (βarr1 and 2) share a high degree of sequence and structural similarity; still, however, they often mediate distinct functional...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.08.053
更新日期:2019-09-24 00:00:00
abstract::In contrast to our extensive knowledge on covalent small ubiquitin-like modifier (SUMO) target proteins, we are limited in our understanding of non-covalent SUMO-binding proteins. We identify interactors of different SUMO isoforms-monomeric SUMO1, monomeric SUMO2, or linear trimeric SUMO2 chains-using a mass spectrome...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2021.108691
更新日期:2021-01-26 00:00:00
abstract::MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks b...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.031
更新日期:2016-01-12 00:00:00
abstract::Meiotic progression in S. pombe is regulated by stage-specific gene expression and translation, changes in RNA stability, expression of anti-sense transcripts, and targeted proteolysis of regulatory proteins. We have used SILAC labeling to examine the relative levels of proteins in diploid S. pombe cells during meiosi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.12.075
更新日期:2019-01-22 00:00:00
abstract::HIV-1 uses the microtubule network to traffic the viral capsid core toward the nucleus. Viral nuclear trafficking and infectivity require the kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with the HIV-1 capsid and specifically binds capsid protein (CA) hexamers. FEZ1 contains multip...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.079
更新日期:2019-08-27 00:00:00
abstract::The chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4(+) T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golg...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.05.015
更新日期:2014-06-26 00:00:00
abstract::The p110β isoform of PI3K is preferentially activated in many tumors deficient in the phosphatase and tensin homolog (PTEN). However, the mechanism(s) linking PTEN loss to p110β activation remain(s) mysterious. Here, we identify CRKL as a member of the class of PI3Kβ-interacting proteins. Silencing CRKL expression in ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.06.054
更新日期:2017-07-18 00:00:00
abstract::The notion that decapping leads irreversibly to messenger RNA (mRNA) decay was contradicted by the identification of capped transcripts missing portions of their 5' ends and a cytoplasmic complex that can restore the cap on uncapped mRNAs. In this study, we used accumulation of uncapped transcripts in cells inhibited ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.07.011
更新日期:2012-09-27 00:00:00
abstract::Although DNA methylation is commonly invoked as a mechanism for transcriptional repression, the extent to which it actively silences transcription factor (TF) occupancy sites in vivo is unknown. To study the role of DNA methylation in the active modulation of TF binding, we quantified the effect of DNA methylation dep...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.07.024
更新日期:2015-08-18 00:00:00