当前位置： SCI文献检索 > MOLECULAR CELL期刊下所有文献 > Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown.

Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown.

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 also activate the other chymotrypsin-like site. Moreover, substrates of the caspase-like sites inhibit allosterically the chymotrypsin-like activity (the rate-limiting one in protein breakdown) and thus can reduce the degradation of proteins by 26S proteasomes. These allosteric effects suggest an ordered, cyclical mechanism for protein degradation. We propose that the chymotrypsin-like site initially cleaves ("bites") the polypeptide, thereby stimulating the caspase-like sites. Their activation accelerates further cleavage ("chewing") of the fragments, while the chymotrypsin-like activity is temporarily inhibited. When further caspase-like cleavages are impossible, the chymotryptic site is reactivated and the cycle repeated.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Kisselev AF,Akopian TN,Castillo V,Goldberg AL

doi

10.1016/s1097-2765(00)80341-x

subject

Has Abstract

pub_date

1999-09-01 00:00:00

pages

395-402

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(00)80341-X

journal_volume

4

pub_type

杂志文章

相关文献

MOLECULAR CELL文献大全
  • A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im.

    abstract：:Human cleavage factor I(m) (CFI(m)) is a heterodimeric RNA binding protein complex that functions at an early step in the assembly of the pre-mRNA 3' processing complex. In this report we show that CFI(m) can stimulate both cleavage and poly(A) addition, and can act to suppress poly(A) site cleavage in a sequence-depe...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00453-2

    authors： Brown KM,Gilmartin GM

    更新日期：2003-12-01 00:00:00

  • Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination.

    abstract：:The Mre11-Rad50-Nbs1 (MRN) complex is a primary sensor of DNA double-strand breaks (DSBs). Upon recruitment to DSBs, it plays a critical role in catalyzing 5' --> 3' single-strand resection that is required for repair by homologous recombination (HR). Unknown mechanisms repress HR in G1 phase of the cell cycle during ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.09.009

    authors： Limbo O,Chahwan C,Yamada Y,de Bruin RA,Wittenberg C,Russell P

    更新日期：2007-10-12 00:00:00

  • Tbf1 or not Tbf1?

    abstract：:In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale shift in the key regulatory protein involved in ribosomal protein (RP) synthesis during the evolution of S. cerevisiae and, en passant, raise interesting questions about the relationship between RP genes and telomeres. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2008.02.008

    authors： Bhattacharya A,Warner JR

    更新日期：2008-03-14 00:00:00

  • Vesicle Tethering on the Surface of Phase-Separated Active Zone Condensates.

    abstract：:Tethering of synaptic vesicles (SVs) to the active zone determines synaptic strength, although the molecular basis governing SV tethering is elusive. Here, we discover that small unilamellar vesicles (SUVs) and SVs from rat brains coat on the surface of condensed liquid droplets formed by active zone proteins RIM, RIM...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2020.10.029

    authors： Wu X,Ganzella M,Zhou J,Zhu S,Jahn R,Zhang M

    更新日期：2021-01-07 00:00:00

  • Essential role for the mammalian ATG8 isoform LC3C in xenophagy.

    abstract：:In this issue, Randow and coworkers (von Muhlinen et al., 2012) report that LC3C plays an essential role in Salmonella clearance by interacting with the autophagic receptor NDP52, with consequent recruitment of all other ATG8 proteins to assist in the buildup of the autophagic membrane. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2012.10.020

    authors： Shpilka T,Elazar Z

    更新日期：2012-11-09 00:00:00

  • Transcriptional ShortCUTs.

    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

    authors： Dichtl B

    更新日期：2008-09-05 00:00:00

  • Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication.

    abstract：:Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency. However, there is only slow removal of uracil from misincorporated dUMP in isolated ung-/- nucle...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80271-3

    authors： Nilsen H,Rosewell I,Robins P,Skjelbred CF,Andersen S,Slupphaug G,Daly G,Krokan HE,Lindahl T,Barnes DE

    更新日期：2000-06-01 00:00:00

  • Methylation of Histone H3K79 by Dot1L Requires Multiple Contacts with the Ubiquitinated Nucleosome.

    abstract：:Cryo-EM structures of Dot1L in complex with a ubiquitinated nucleosome provide the long-sought-after molecular mechanism of Dot1L-mediated methylation of lysine 79 in histone H3 and explain crosstalk with histone H2B ubiquitination. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2019.05.013

    authors： Zhang Y,Kutateladze TG

    更新日期：2019-06-06 00:00:00

  • Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells.

    abstract：:The Ca2+ -activated K+ channel KCa3.1 is required for Ca2+ influx and the subsequent activation of B and T cells. Inhibitors of KCa3.1 are in development to treat autoimmune diseases and transplant rejection, underscoring the importance in understanding how these channels are regulated. We show that nucleoside diphosp...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2006.11.012

    authors： Srivastava S,Li Z,Ko K,Choudhury P,Albaqumi M,Johnson AK,Yan Y,Backer JM,Unutmaz D,Coetzee WA,Skolnik EY

    更新日期：2006-12-08 00:00:00

  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

    abstract：:β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.07.036

    authors： Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

    更新日期：2018-09-20 00:00:00

  • Unfaithful DNA polymerase caught in the act.

    abstract：:The 3D structures of all 12 mispairs formed in the active site of a DNA polymerase help explain their differential effects on polymerase stalling and on translocation of the primer terminus to the enzyme's proofreading site. ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(04)00149-2

    authors： Jiricny J

    更新日期：2004-03-26 00:00:00

  • A role for TBP dimerization in preventing unregulated gene expression.

    abstract：:The recruitment of the TATA box-binding protein (TBP) to promoters in vivo is often rate limiting in gene expression. We present evidence that TBP negatively autoregulates its accessibility to promoter DNA in yeast through dimerization. The crystal structure of TBP dimers was used to design point mutations in the dime...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(01)80004-6

    authors： Jackson-Fisher AJ,Chitikila C,Mitra M,Pugh BF

    更新日期：1999-06-01 00:00:00

  • MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype.

    abstract：:Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism typified by stable proliferative arrest, a persistent DNA damage response, and the senescence-associated secretory phenotype (SASP), which helps to maintain the senescent state and triggers bystander senescence in a paracrine fashion. Here, we demonstr...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2015.07.011

    authors： Chen H,Ruiz PD,McKimpson WM,Novikov L,Kitsis RN,Gamble MJ

    更新日期：2015-09-03 00:00:00

  • A Multiplexed Assay for Exon Recognition Reveals that an Unappreciated Fraction of Rare Genetic Variants Cause Large-Effect Splicing Disruptions.

    abstract：:Mutations that lead to splicing defects can have severe consequences on gene function and cause disease. Here, we explore how human genetic variation affects exon recognition by developing a multiplexed functional assay of splicing using Sort-seq (MFASS). We assayed 27,733 variants in the Exome Aggregation Consortium ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.10.037

    authors： Cheung R,Insigne KD,Yao D,Burghard CP,Wang J,Hsiao YE,Jones EM,Goodman DB,Xiao X,Kosuri S

    更新日期：2019-01-03 00:00:00

  • Formation of a novel four-helix bundle and molecular recognition sites by dimerization of a response regulator phosphotransferase.

    abstract：:A basis for understanding specificity of molecular recognition between phosphorelay proteins has been deduced from the 2.6 A structure of the Spo0B phosphotransferase of the phosphorelay regulating sporulation initiation. Spo0B consists of two domains: an N-terminal alpha-helical hairpin domain and a C-terminal alpha/...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80148-3

    authors： Varughese KI,Madhusudan,Zhou XZ,Whiteley JM,Hoch JA

    更新日期：1998-10-01 00:00:00

  • Dynamic RNA modifications in posttranscriptional regulation.

    abstract：:Cellular RNAs can be chemically modified over a hundred different ways. These modifications were once thought to be static, discrete, and utilized to fine-tune RNA structure and function. However, recent studies have revealed that some modifications, like mRNA methylation, can be reversed, and these reversible modific...

    journal_title：Molecular cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.molcel.2014.09.001

    authors： Wang X,He C

    更新日期：2014-10-02 00:00:00

  • Crossover and noncrossover pathways in mouse meiosis.

    abstract：:During meiosis, recombination between homologous chromosomes generates crossover (CR) and noncrossover (NCR) products. CRs establish connections between homologs, whereas intermediates leading to NCRs have been proposed to participate in homologous pairing. How these events are differentiated and regulated remains to ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2005.09.021

    authors： Guillon H,Baudat F,Grey C,Liskay RM,de Massy B

    更新日期：2005-11-23 00:00:00

  • High-Resolution Mapping of Multiway Enhancer-Promoter Interactions Regulating Pathogen Detection.

    abstract：:Eukaryotic gene expression regulation involves thousands of distal regulatory elements. Understanding the quantitative contribution of individual enhancers to gene expression is critical for assessing the role of disease-associated genetic risk variants. Yet, we lack the ability to accurately link genes with their dis...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2020.09.005

    authors： Vangala P,Murphy R,Quinodoz SA,Gellatly K,McDonel P,Guttman M,Garber M

    更新日期：2020-10-15 00:00:00

  • Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3.

    abstract：:The eukaryotic RNA exosome is an essential and conserved 3'-to-5' exoribonuclease complex that degrades or processes nearly every class of cellular RNA. The nuclear RNA exosome includes a 9-subunit non-catalytic core that binds Rrp44 (Dis3) and Rrp6 subunits to modulate their processive and distributive 3'-to-5' exori...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2016.09.038

    authors： Zinder JC,Wasmuth EV,Lima CD

    更新日期：2016-11-17 00:00:00

  • Cdh1 is a HECT of an activator.

    abstract：:Cdh1 is a well-established activator of APC/C, a RING-type ubiquitin ligase. In this issue of Molecular Cell, Wan et al. (2011) report an APC/C-independent role of Cdh1 during development as an activator for Smurf1, a HECT-type ubiquitin ligase. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2011.11.012

    authors： Jia L,Yu H

    更新日期：2011-12-09 00:00:00

  • The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1.

    abstract：:Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals a...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2017.05.026

    authors： Flury V,Georgescu PR,Iesmantavicius V,Shimada Y,Kuzdere T,Braun S,Bühler M

    更新日期：2017-07-20 00:00:00

  • Y14 and hUpf3b form an NMD-activating complex.

    abstract：:Messenger RNAs with premature translation termination codons (PTCs) are degraded by nonsense-mediated mRNA decay (NMD). In mammals, PTCs are discriminated from physiological stop codons by a process thought to involve the splicing-dependent deposition of an exon junction complex (EJC), EJC-mediated recruitment of Upf3...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00142-4

    authors： Gehring NH,Neu-Yilik G,Schell T,Hentze MW,Kulozik AE

    更新日期：2003-04-01 00:00:00

  • Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain.

    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

    authors： Peyroche A,Antonny B,Robineau S,Acker J,Cherfils J,Jackson CL

    更新日期：1999-03-01 00:00:00

  • Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres.

    abstract：:Genome stability depends upon the RecQ helicases, which are conserved from bacteria to man, but little is known about how their myriad activities are regulated. Fission yeast lacking the telomere protein Taz1 (mammalian TRF1/TRF2 ortholog) lose many hallmarks of telomeres, including accurate replication and local prot...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2009.01.027

    authors： Rog O,Miller KM,Ferreira MG,Cooper JP

    更新日期：2009-03-13 00:00:00

  • Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer.

    abstract：:Alternative mRNA splicing of the fibronectin EDI exon is controlled by a purine-rich exonic splicing enhancer (ESE), postulated as a binding site for SR proteins. By using a transient expression alternative splicing assay combined with promoter swapping, we have demonstrated that the promoter can also control EDI spli...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80372-x

    authors： Cramer P,Cáceres JF,Cazalla D,Kadener S,Muro AF,Baralle FE,Kornblihtt AR

    更新日期：1999-08-01 00:00:00

  • Histone Deacetylase 3 Couples Mitochondria to Drive IL-1β-Dependent Inflammation by Configuring Fatty Acid Oxidation.

    abstract：:Immune cell function depends on specific metabolic programs dictated by mitochondria, including nutrient oxidation, macromolecule synthesis, and post-translational modifications. Mitochondrial adaptations have been linked to acute and chronic inflammation, but the metabolic cues and precise mechanisms remain unclear. ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2020.08.015

    authors： Chi Z,Chen S,Xu T,Zhen W,Yu W,Jiang D,Guo X,Wang Z,Zhang K,Li M,Zhang J,Fang H,Yang D,Ye Q,Yang X,Lin H,Yang F,Zhang X,Wang D

    更新日期：2020-10-01 00:00:00

  • Retracted: Histone H2B ubquitination regulates retinoic acid signaling through the cooperation of ASXL1 and BAP1.

    abstract：:Despite the importance of retinoic acid (RA) signaling and histone monoubiquitination in determining cell fate, the underlying mechanism linking the two processes is poorly explored. We describe that additional sex comb-like 1 (ASXL1) represses RA receptor activity by cooperating with BRCA1-associated protein 1 (BAP1)...

    journal_title：Molecular cell

    pub_type： 杂志文章,收录出版

    doi：10.1016/j.molcel.2013.06.005

    authors： Lee SW,Youn H,Kim EJ,Um SJ

    更新日期：2013-07-25 00:00:00

  • Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O.

    abstract：:The tumor suppressor BAP1 interacts with chromatin-associated proteins and regulates cell proliferation, but its mechanism of action and regulation remain poorly defined. We show that the ubiquitin-conjugating enzyme UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2014.03.002

    authors： Mashtalir N,Daou S,Barbour H,Sen NN,Gagnon J,Hammond-Martel I,Dar HH,Therrien M,Affar el B

    更新日期：2014-05-08 00:00:00

  • Autophagic Degradation of the 26S Proteasome Is Mediated by the Dual ATG8/Ubiquitin Receptor RPN10 in Arabidopsis.

    abstract：:Autophagic turnover of intracellular constituents is critical for cellular housekeeping, nutrient recycling, and various aspects of growth and development in eukaryotes. Here we show that autophagy impacts the other major degradative route involving the ubiquitin-proteasome system by eliminating 26S proteasomes, a pro...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2015.04.023

    authors： Marshall RS,Li F,Gemperline DC,Book AJ,Vierstra RD

    更新日期：2015-06-18 00:00:00

  • An acid test for g proteins.

    abstract：:In this issue, Isom et al. (2013) report their exciting discovery that G proteins can sense pH changes to fine-tune signaling in response to metabolic changes. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2013.08.012

    authors： Sprang SR

    更新日期：2013-08-22 00:00:00