Abstract：
:Autophagy, a catabolic pathway that delivers cellular components to lysosomes for degradation, can be activated by stressful conditions such as nutrient starvation and endoplasmic reticulum (ER) stress. We report that thapsigargin, an ER stressor widely used to induce autophagy, in fact blocks autophagy. Thapsigargin does not affect autophagosome formation but leads to accumulation of mature autophagosomes by blocking autophagosome fusion with the endocytic system. Strikingly, thapsigargin has no effect on endocytosis-mediated degradation of epidermal growth factor receptor. Molecularly, while both Rab7 and Vps16 are essential regulatory components for endocytic fusion with lysosomes, we found that Rab7 but not Vps16 is required for complete autophagy flux, and that thapsigargin blocks recruitment of Rab7 to autophagosomes. Therefore, autophagosomal-lysosomal fusion must be governed by a distinct molecular mechanism compared to general endocytic fusion.
journal_name
Mol Celljournal_title
Molecular cellauthors
Ganley IG,Wong PM,Gammoh N,Jiang Xdoi
10.1016/j.molcel.2011.04.024subject
Has Abstractpub_date
2011-06-24 00:00:00pages
731-43issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00370-4journal_volume
42pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract：:Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryp...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.08.030
更新日期：2018-11-01 00:00:00
abstract：:The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2011.03.025
更新日期：2011-05-06 00:00:00
abstract：:During X-inactivation, Xist RNA spreads along an entire chromosome to establish silencing. However, the mechanism and functional RNA elements involved in spreading remain undefined. By performing a comprehensive endogenous Xist deletion screen, we identify Repeat B as crucial for spreading Xist and maintaining Polycom...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2019.01.015
更新日期：2019-04-04 00:00:00
abstract：:We have analyzed two residues in the helicase domain of the E1 initiator protein. These residues are part of a highly conserved structural motif, the beta-hairpin, which is present in the helicase domain of all papovavirus initiator proteins. These proteins are unique in their ability to transition from local template...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2007.02.009
更新日期：2007-03-23 00:00:00
abstract：:Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2008.08.014
更新日期：2008-09-05 00:00:00
abstract：:We generated knockout mice for MCM8 and MCM9 and show that deficiency for these genes impairs homologous recombination (HR)-mediated DNA repair during gametogenesis and somatic cells cycles. MCM8(-/-) mice are sterile because spermatocytes are blocked in meiotic prophase I, and females have only arrested primary folli...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.05.048
更新日期：2012-08-24 00:00:00
abstract：:We demonstrate that the major in vivo targets of brefeldin A (BFA) in the secretory pathway of budding yeast are the three members of the Sec7 domain family of ARF exchange factors: Gea1p and Gea2p (functionally interchangeable) and Sec7p. Specific residues within the Sec7 domain are important for BFA inhibition of AR...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80455-4
更新日期：1999-03-01 00:00:00
abstract：:The membrane-spanning C-terminal regions in tail-anchored proteins must be recognized and delivered posttranslationally to the endoplasmic reticulum or mitochondrial membrane. A paper in this issue of Molecular Cell (Wang et al., 2010) and another recent report (Mariappan et al., 2010) delineate early steps in this pa...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.09.016
更新日期：2010-10-08 00:00:00
abstract：:The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s) remain largely unknown. Here, we repo...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.08.016
更新日期：2010-09-10 00:00:00
abstract：:Communication between the 5' cap structure and 3' poly(A) tail of eukaryotic mRNA results in the synergistic enhancement of translation. The cap and poly(A) tail binding proteins, eIF4E and Pab1p, mediate this effect in the yeast S. cerevisiae through their interactions with different parts of the translation factor e...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80122-7
更新日期：1998-07-01 00:00:00
abstract：:Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The X-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based m...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.07.013
更新日期：2009-09-11 00:00:00
abstract：:The structure of an RNA polymerase II/general transcription factor TFIIF complex was determined by cryo-electron microscopy and single particle analysis. Density due to TFIIF was not concentrated in one area but rather was widely distributed across the surface of the polymerase. The largest subunit of TFIIF interacted...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(03)00387-3
更新日期：2003-10-01 00:00:00
abstract：:Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2020.02.001
更新日期：2020-04-02 00:00:00
abstract：:2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, elicitin...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2019.05.006
更新日期：2019-07-25 00:00:00
abstract：:Cardozo Gizzi et al. (2019) develop a new sequential imaging methodology (Hi-M) for observing chromosome structure in the Drosophila blastoderm and find that topological domains in single nuclei change in response to transcriptional activation. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2019.03.017
更新日期：2019-04-04 00:00:00
abstract：:In this issue of Molecular Cell, Yang et al. (2011) demonstrate that Aurora B phosphorylates ATM, leading to its mitotic activation and ability to phosphorylate Bub1 and regulate the spindle checkpoint, thus maintaining genomic integrity. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2011.11.001
更新日期：2011-11-18 00:00:00
abstract：:ER-associated degradation (ERAD) of glycoproteins depends on dual recognition of protein misfolding and remodeling of the substrate's N-linked glycans. After recognition, substrates are retrotranslocated to the cytosol for proteasomal degradation. To explore the directionality of this process, we fused a highly stable...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.07.027
更新日期：2005-09-16 00:00:00
abstract：:The HECT E3 ligases ubiquitinate numerous transcription factors and signaling molecules, and their activity must be tightly controlled to prevent cancer, immune disorders, and other diseases. In this study, we have found unexpectedly that peptide linkers tethering WW domains in several HECT family members are key regu...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2017.03.020
更新日期：2017-05-04 00:00:00
abstract：:In eukaryotes, the 20S proteasome contains two chymotrypsin-like, two trypsin-like, and two active sites shown here to have caspase-like specificity. We report that certain sites allosterically regulate each other's activities. Substrates of a chymotrypsin-like site stimulate dramatically the caspase-like activity and...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80341-x
更新日期：1999-09-01 00:00:00
abstract：:The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas nuclease system is a powerful tool for genome editing, and its simple programmability has enabled high-throughput genetic and epigenetic studies. These high-throughput approaches offer investigators a toolkit for functional interrogation of not...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2017.09.017
更新日期：2017-10-05 00:00:00
abstract：:MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.10.002
更新日期：2012-12-14 00:00:00
abstract：:The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanisticall...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2020.02.005
更新日期：2020-04-16 00:00:00
abstract：:In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S p...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.01.014
更新日期：2005-02-18 00:00:00
abstract：:The G protein-coupled receptor Gpr1 and associated Galpha subunit Gpa2 govern dimorphic transitions in response to extracellular nutrients by signaling coordinately with Ras to activate adenylyl cyclase in the yeast Saccharomyces cerevisiae. Gpa2 forms a protein complex with the kelch Gbeta mimic subunits Gpb1/2, and ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.05.011
更新日期：2006-06-23 00:00:00
abstract：:Allosteric communication between interacting molecules is fundamental to signal transduction and many other cellular processes. To better understand the relationship between nuclear receptor (NR) ligand positioning and the formation of the coactivator binding pocket, we investigated the determinants of ligand selectiv...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(04)00054-1
更新日期：2004-02-13 00:00:00
abstract：:We have used EM visualization of active genes on plasmid vectors in Xenopus oocyte nuclei to investigate the relationship between poly(A) signals and RNA polymerase II transcription termination. Although a functional poly(A) signal is required for efficient termination, cotranscriptional RNA cleavage at the poly(A) si...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80465-7
更新日期：1999-03-01 00:00:00
abstract：:Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2008.07.004
更新日期：2008-08-08 00:00:00
abstract：:The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation, whereas FGF-10 pro...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2013.08.002
更新日期：2013-09-26 00:00:00
abstract：:Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2016.04.032
更新日期：2016-06-16 00:00:00
abstract：:Posttranslational modification with small ubiquitin-related modifier (SUMO) has emerged as a central regulatory mechanism of protein function. However, little is known about the regulation of sumoylation itself. It has been reported that it is increased after exposure to various stresses including strong oxidative str...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.12.019
更新日期：2006-02-03 00:00:00
