Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.

Abstract:

:Conjugation of ubiquitin-like protein Nedd8 to cullins (neddylation) is essential for the function of cullin-RING ubiquitin ligases (CRLs). Here, we show that neddylation stimulates CRL activity by multiple mechanisms. For the initiator ubiquitin, the major effect is to bridge the approximately 50 A gap between naked substrate and E2 approximately Ub bound to SCF. The gap between the acceptor lysine of ubiquitinated substrate and E2 approximately Ub is much smaller, and, consequentially, the impact of neddylation on transfer of subsequent ubiquitins by Cdc34 arises primarily from improved E2 recruitment and enhanced amide bond formation in the E2 active site. The combined effects of neddylation greatly enhance the probability that a substrate molecule acquires >or= 4 ubiquitins in a single encounter with a CRL. The surprisingly diverse effects of Nedd8 conjugation underscore the complexity of CRL regulation and suggest that modification of other ubiquitin ligases with ubiquitin or ubiquitin-like proteins may likewise have major functional consequences.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Saha A,Deshaies RJ

doi

10.1016/j.molcel.2008.08.021

subject

Has Abstract

pub_date

2008-10-10 00:00:00

pages

21-31

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00609-6

journal_volume

32

pub_type

杂志文章
  • ATPase site architecture is required for self-assembly and remodeling activity of a hexameric AAA+ transcriptional activator.

    abstract::AAA+ proteins (ATPases associated with various cellular activities) are oligomeric ATPases that use ATP hydrolysis to remodel their substrates. By similarity with GTPases, a dynamic organization of the nucleotide-binding pockets between ATPase protomers is proposed to regulate functionality. Using the transcription ac...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.06.012

    authors: Joly N,Zhang N,Buck M

    更新日期:2012-08-10 00:00:00

  • Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.

    abstract::The protein kinase B-RAF is mutated in approximately 7% of human cancers. Most mutations are activating, but, surprisingly, a small number have reduced kinase activity. However, the latter can still stimulate cellular signaling through the MEK-ERK pathway because they activate the related family member C-RAF. We exami...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.10.022

    authors: Garnett MJ,Rana S,Paterson H,Barford D,Marais R

    更新日期:2005-12-22 00:00:00

  • PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity.

    abstract::PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.03.010

    authors: Zhou B,Wang J,Lee SY,Xiong J,Bhanu N,Guo Q,Ma P,Sun Y,Rao RC,Garcia BA,Hess JL,Dou Y

    更新日期:2016-04-21 00:00:00

  • Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish.

    abstract::The control of mRNA stability plays a central role in regulating gene expression. In metazoans, the earliest stages of development are driven by maternally supplied mRNAs. The degradation of these maternal mRNAs is critical for promoting the maternal-to-zygotic transition of developmental programs, although the underl...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.02.027

    authors: Mishima Y,Tomari Y

    更新日期:2016-03-17 00:00:00

  • Dynamics of enhancer-promoter communication during differentiation-induced gene activation.

    abstract::We analyzed the order of recruitment of factors to the HNF-4alpha regulatory regions upon the initial activation of the gene during enterocyte differentiation. An initially independent assembly of regulatory complexes at the proximal promoter and the upstream enhancer regions was followed by the tracking of the entire...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00786-4

    authors: Hatzis P,Talianidis I

    更新日期:2002-12-01 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

  • A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.

    abstract::Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identif...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.12.026

    authors: Wang J,Grubb LE,Wang J,Liang X,Li L,Gao C,Ma M,Feng F,Li M,Li L,Zhang X,Yu F,Xie Q,Chen S,Zipfel C,Monaghan J,Zhou JM

    更新日期:2018-02-01 00:00:00

  • Guide RNA functional modules direct Cas9 activity and orthogonality.

    abstract::The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a sequence-dependent manner and has been widely used for programmable genome editing. Cas9 activity is dependent on interactions with guide RNAs, and evolutionarily divergent Cas9 nucleases have been shown to work orthogonally. However, the molec...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.09.019

    authors: Briner AE,Donohoue PD,Gomaa AA,Selle K,Slorach EM,Nye CH,Haurwitz RE,Beisel CL,May AP,Barrangou R

    更新日期:2014-10-23 00:00:00

  • The response regulator BvgA and RNA polymerase alpha subunit C-terminal domain bind simultaneously to different faces of the same segment of promoter DNA.

    abstract::Examination of the binding of FeBABE-conjugated BvgA to the fha promoter of Bordetella pertussis has revealed that three dimers, formed by head-to-head association of monomers, bind one face of the DNA helix from the inverted-heptad primary binding site to the -35 region. The orientation of BvgA monomers within the di...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00007-8

    authors: Boucher PE,Maris AE,Yang MS,Stibitz S

    更新日期:2003-01-01 00:00:00

  • Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-gamma-stimulated brain astrocytes.

    abstract::To unravel the roles of LXRs in inflammation and immunity, we examined the function of LXRs in development of IFN-gamma-mediated inflammation using cultured rat brain astrocytes. LXR ligands inhibit neither STAT1 phosphorylation nor STAT1 translocation to the nucleus but, rather, inhibit STAT1 binding to promoters and...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.07.021

    authors: Lee JH,Park SM,Kim OS,Lee CS,Woo JH,Park SJ,Joe EH,Jou I

    更新日期:2009-09-24 00:00:00

  • The Sjögren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.

    abstract::Sphingosine 1-phosphate (S1P) functions not only as a bioactive lipid molecule, but also as an important intermediate of the sole sphingolipid-to-glycerolipid metabolic pathway. However, the precise reactions and the enzymes involved in this pathway remain unresolved. We report here that yeast HFD1 and the Sjögren-Lar...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.04.033

    authors: Nakahara K,Ohkuni A,Kitamura T,Abe K,Naganuma T,Ohno Y,Zoeller RA,Kihara A

    更新日期:2012-05-25 00:00:00

  • Hijacked by an oocyte: hierarchical molecular changes in somatic cell nuclear transfer.

    abstract::Xenopus oocytes can epigenetically reprogram mouse somatic cells toward totipotency. In this issue, Jullien et al. (2014) now describe rapid, interdependent molecular events that facilitate this reprogramming. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2014.08.008

    authors: Maza I,Hanna JH

    更新日期:2014-08-21 00:00:00

  • A splicing-independent function of SF2/ASF in microRNA processing.

    abstract::Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upr...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.02.021

    authors: Wu H,Sun S,Tu K,Gao Y,Xie B,Krainer AR,Zhu J

    更新日期:2010-04-09 00:00:00

  • Stopping the Clock with MYC.

    abstract::In a recent paper in Cell Metabolism, Altman et al. (2015) report that MYC disrupts the molecular clock in cancer cells and describe a link between oncogenesis, circadian rhythms, and metabolism. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2015.11.008

    authors: Lau AN,Vander Heiden MG

    更新日期:2015-11-19 00:00:00

  • Facultative heterochromatin: is there a distinctive molecular signature?

    abstract::The Latin word "facultas" literally means "opportunity." Facultative heterochromatin (fHC) then designates genomic regions in the nucleus of a eukaryotic cell that have the opportunity to adopt open or compact conformations within temporal and spatial contexts. This review focuses on the molecular and functional aspec...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2007.09.011

    authors: Trojer P,Reinberg D

    更新日期:2007-10-12 00:00:00

  • A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage.

    abstract::In this study, we used Saccharomyces cerevisiae to identify a biological network that prevents the deleterious effects of endogenous reactive oxygen species. The absence of Tsa1, a key peroxiredoxin, caused increased rates of mutations, chromosomal rearrangements, and recombination. Defects in recombinational DNA doub...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.02.008

    authors: Huang ME,Kolodner RD

    更新日期:2005-03-04 00:00:00

  • Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling.

    abstract::Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-kappaB signaling pathways-IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-n...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.12.036

    authors: Paquette N,Broemer M,Aggarwal K,Chen L,Husson M,Ertürk-Hasdemir D,Reichhart JM,Meier P,Silverman N

    更新日期:2010-01-29 00:00:00

  • Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells.

    abstract::Heterochromatin is required to restrict aberrant expression of retrotransposons, but it remains poorly defined due to the underlying repeat-rich sequences. We dissected Suv39h-dependent histone H3 lysine 9 trimethylation (H3K9me3) by genome-wide ChIP sequencing in mouse embryonic stem cells (ESCs). Refined bioinformat...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.05.029

    authors: Bulut-Karslioglu A,De La Rosa-Velázquez IA,Ramirez F,Barenboim M,Onishi-Seebacher M,Arand J,Galán C,Winter GE,Engist B,Gerle B,O'Sullivan RJ,Martens JH,Walter J,Manke T,Lachner M,Jenuwein T

    更新日期:2014-07-17 00:00:00

  • E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1.

    abstract::Ubiquitination typically occurs through the sequential action of three enzymes catalyzing ubiquitin activation (E1), conjugation (E2), and ligation (E3) and regulates diverse eukaryotic cellular processes. Although monoubiquitination commonly confers nondegradative activities, mechanisms underlying its temporal and sp...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.04.022

    authors: Sun L,Fang J

    更新日期:2016-06-16 00:00:00

  • A Dicer-Independent Route for Biogenesis of siRNAs that Direct DNA Methylation in Arabidopsis.

    abstract::DNA methylation directed by 24-nucleotide (nt) small interfering RNAs (siRNAs) plays critical roles in gene regulation and transposon silencing in Arabidopsis. 24-nt siRNAs are known to be processed from double-stranded RNAs by Dicer-like 3 (DCL3) and loaded into the effector Argonaute 4 (AGO4). Here we report a disti...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.11.015

    authors: Ye R,Chen Z,Lian B,Rowley MJ,Xia N,Chai J,Li Y,He XJ,Wierzbicki AT,Qi Y

    更新日期:2016-01-21 00:00:00

  • Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p.

    abstract::Activation of retrograde signaling (RS) by mitochondrial dysfunction or by inhibition of TOR kinases in yeast results in nuclear accumulation of the transcription factors, Rtg1p and Rtg3p. This process requires Rtg2p, a novel cytoplasmic protein with an N-terminal ATP binding domain. We show that Rtg2p controls RS by ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00285-5

    authors: Liu Z,Sekito T,Spírek M,Thornton J,Butow RA

    更新日期:2003-08-01 00:00:00

  • Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting.

    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

    authors: Loeb GB,Khan AA,Canner D,Hiatt JB,Shendure J,Darnell RB,Leslie CS,Rudensky AY

    更新日期:2012-12-14 00:00:00

  • Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor.

    abstract::Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains s...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00469-0

    authors: Fiorini E,Schmitz I,Marissen WE,Osborn SL,Touma M,Sasada T,Reche PA,Tibaldi EV,Hussey RE,Kruisbeek AM,Reinherz EL,Clayton LK

    更新日期:2002-03-01 00:00:00

  • PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.

    abstract::Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.10.013

    authors: Dawicki-McKenna JM,Langelier MF,DeNizio JE,Riccio AA,Cao CD,Karch KR,McCauley M,Steffen JD,Black BE,Pascal JM

    更新日期:2015-12-03 00:00:00

  • Magic Acts with the Cohesin Ring.

    abstract::Recent studies, including two in this issue of Molecular Cell (Elbatsh et al., 2016; Beckouët et al., 2016), cast light on how cohesin regulators harness the energy of ATP hydrolysis to open the cohesin ring and enable dynamic, regulated entrapment of chromosomes. ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.02.003

    authors: Yu H

    更新日期:2016-02-18 00:00:00

  • MicroRNAs cross the line: the battle for mRNA stability enters the coding sequence.

    abstract::A study in this issue of Molecular Cell (Elcheva et al., 2009) shows the inherent instability of the betaTrCP1 mRNA to be caused by microRNA-183 targeting the coding sequence; interestingly, this action is directly opposed by the RNA-binding protein CRD-BP. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2009.07.006

    authors: Nielsen AF,Gloggnitzer J,Martinez J

    更新日期:2009-07-31 00:00:00

  • Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.

    abstract::A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we s...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.01.016

    authors: Giorgetti L,Siggers T,Tiana G,Caprara G,Notarbartolo S,Corona T,Pasparakis M,Milani P,Bulyk ML,Natoli G

    更新日期:2010-02-12 00:00:00

  • An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.

    abstract::Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to pre...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.07.023

    authors: Worden EJ,Dong KC,Martin A

    更新日期:2017-09-07 00:00:00

  • Activation of a primed RING E3-E2-ubiquitin complex by non-covalent ubiquitin.

    abstract::RING ubiquitin ligases (E3) recruit ubiquitin-conjugate enzymes (E2) charged with ubiquitin (Ub) to catalyze ubiquitination. Non-covalent Ub binding to the backside of certain E2s promotes processive polyUb formation, but the mechanism remains elusive. Here, we show that backside bound Ub (Ub(B)) enhances both RING-in...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.02.017

    authors: Buetow L,Gabrielsen M,Anthony NG,Dou H,Patel A,Aitkenhead H,Sibbet GJ,Smith BO,Huang DT

    更新日期:2015-04-16 00:00:00

  • Yeast unravels epigenetic apoptosis control: deadly chat within a histone tail.

    abstract::An important paper by David Allis and colleagues (Ahn et al., 2006 [this issue of Molecular Cell]) describes a specific deacetylation/phosphorylation crosstalk at the histone H2B tail required for apoptosis induction in yeast, thus giving first insights into the poorly understood epigenetic regulation of cell death. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.molcel.2006.10.004

    authors: Carmona-Gutierrez D,Madeo F

    更新日期:2006-10-20 00:00:00