Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex.

Abstract:

:The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs--predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor.

journal_name

Mol Cell

journal_title

Molecular cell

authors

He J,Chao WC,Zhang Z,Yang J,Cronin N,Barford D

doi

10.1016/j.molcel.2013.04.024

subject

Has Abstract

pub_date

2013-06-06 00:00:00

pages

649-60

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(13)00329-8

journal_volume

50

pub_type

杂志文章
  • Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β1-Adrenergic Receptor.

    abstract::Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β1-adrenergic receptor (β1-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β1-ARs, leading to in...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.08.001

    authors: Su M,Zhu L,Zhang Y,Paknejad N,Dey R,Huang J,Lee MY,Williams D,Jordan KD,Eng ET,Ernst OP,Meyerson JR,Hite RK,Walz T,Liu W,Huang XY

    更新日期:2020-10-01 00:00:00

  • Repair of UV-Induced DNA Damage Independent of Nucleotide Excision Repair Is Masked by MUTYH.

    abstract::DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defec...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.10.021

    authors: Mazouzi A,Battistini F,Moser SC,Ferreira da Silva J,Wiedner M,Owusu M,Lardeau CH,Ringler A,Weil B,Neesen J,Orozco M,Kubicek S,Loizou JI

    更新日期:2017-11-16 00:00:00

  • Targeting UBE4A Revives Viperin Protein in Epithelium to Enhance Host Antiviral Defense.

    abstract::Mutation and prevalence of pathogenic viruses prompt the development of broad-spectrum antiviral strategies. Viperin is a potent antiviral protein that inhibits a broad range of viruses. Unexpectedly, we found that Viperin protein production in epithelium is defective in response to both viruses and interferons (IFNs)...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2019.11.003

    authors: Yuan Y,Miao Y,Qian L,Zhang Y,Liu C,Liu J,Zuo Y,Feng Q,Guo T,Zhang L,Chen X,Jin L,Huang F,Zhang H,Zhang W,Li W,Xu G,Zheng H

    更新日期:2020-02-20 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

  • ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.

    abstract::Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechan...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.04.021

    authors: Turakhiya A,Meyer SR,Marincola G,Böhm S,Vanselow JT,Schlosser A,Hofmann K,Buchberger A

    更新日期:2018-06-07 00:00:00

  • ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin.

    abstract::Ataxia Telangiectasia Mutated (ATM) signaling is essential for the repair of a subset of DNA double-strand breaks (DSBs); however, its precise role is unclear. Here, we show that < or =25% of DSBs require ATM signaling for repair, and this percentage correlates with increased chromatin but not damage complexity. Impor...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.05.017

    authors: Goodarzi AA,Noon AT,Deckbar D,Ziv Y,Shiloh Y,Löbrich M,Jeggo PA

    更新日期:2008-07-25 00:00:00

  • Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface.

    abstract::The ER-mitochondrial junction provides a local calcium signaling domain that is critical for both matching energy production with demand and the control of apoptosis. Here, we visualize ER-mitochondrial contact sites and monitor the localized [Ca(2+)] changes ([Ca(2+)](ER-mt)) using drug-inducible fluorescent interorg...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.06.029

    authors: Csordás G,Várnai P,Golenár T,Roy S,Purkins G,Schneider TG,Balla T,Hajnóczky G

    更新日期:2010-07-09 00:00:00

  • Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking.

    abstract::Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer, where it is a key therapeutic target. Here we report that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes ri...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.07.018

    authors: Wang Q,Carroll JS,Brown M

    更新日期:2005-09-02 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

  • How Arabidopsis Talks to Itself about Its Water Supply.

    abstract::Takahashi et al. (2018) report that the peptide CLE25 together with the BAM1, BAM3 LRR receptor-like kinases are involved in root-to-shoot communication during dehydration stress in Arabidopsis. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.06.011

    authors: McLachlan DH,Pridgeon AJ,Hetherington AM

    更新日期:2018-06-21 00:00:00

  • A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.

    abstract::YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2019.06.010

    authors: Zhu C,Li L,Zhang Z,Bi M,Wang H,Su W,Hernandez K,Liu P,Chen J,Chen M,Huang TH,Chen L,Liu Z

    更新日期:2019-08-22 00:00:00

  • Propagating prions in fungi and mammals.

    abstract::Prions constitute a rare class of protein, which can switch to a robust amyloid form and then propagate that form in the absence of a nucleic acid determinant, thereby creating a unique, protein-only infectious agent. Details of the mechanism that drives conversion to the prion form and then subsequent propagation of ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2004.05.012

    authors: Tuite MF,Koloteva-Levin N

    更新日期:2004-06-04 00:00:00

  • PML, SUMO, and RNF4: guardians of nuclear protein quality.

    abstract::In this issue of Molecular Cell, Guo et al. (2014) report that misfolded or aggregated nuclear proteins, such as pathogenic polyQ proteins, are cleared by a SUMO-dependent quality control pathway, which involves the E3 SUMO ligase PML and the SUMO-targeted ubiquitin ligase RNF4. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2014.06.022

    authors: Gärtner A,Muller S

    更新日期:2014-07-03 00:00:00

  • Organization of core spliceosomal components U5 snRNA loop I and U4/U6 Di-snRNP within U4/U6.U5 Tri-snRNP as revealed by electron cryomicroscopy.

    abstract::In eukaryotes, pre-mRNA exons are interrupted by large noncoding introns. Alternative selection of exons and nucleotide-exact removal of introns are performed by the spliceosome, a highly dynamic macromolecular machine. U4/U6.U5 tri-snRNP is the largest and most conserved building block of the spliceosome. By 3D elect...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.08.021

    authors: Sander B,Golas MM,Makarov EM,Brahms H,Kastner B,Lührmann R,Stark H

    更新日期:2006-10-20 00:00:00

  • L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.

    abstract::We have identified human MBT domain-containing protein L3MBTL2 as an integral component of a protein complex that we termed Polycomb repressive complex 1 (PRC1)-like 4 (PRC1L4), given the copresence of PcG proteins RING1, RING2, and PCGF6/MBLR. PRC1L4 also contained E2F6 and CBX3/HP1γ, known to function in transcripti...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.04.004

    authors: Trojer P,Cao AR,Gao Z,Li Y,Zhang J,Xu X,Li G,Losson R,Erdjument-Bromage H,Tempst P,Farnham PJ,Reinberg D

    更新日期:2011-05-20 00:00:00

  • An argonaute protein directs nuclear Xrn2 function.

    abstract::Argonaute proteins are the mediators of small RNA-guided gene silencing pathways. In this issue, Couvillion and coworkers (Couvillion et al., 2012) found an unexpected function for a Tetrahymena Argonaute protein: It forms a complex with tRNA fragments and is required for nuclear Xrn2 localization and function. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2012.11.015

    authors: Hasler D,Meister G

    更新日期:2012-11-30 00:00:00

  • A new twist on clock protein phosphorylation: a conformational change leads to protein degradation.

    abstract::Progressive phosphorylation of circadian clock proteins is a hallmark of time-keeping. In this issue of Molecular Cell, Querfurth et al. (2011) demonstrate that phosphorylation of Neurospora FRQ induces a conformational change, which can account for its temporally gated degradation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2011.08.015

    authors: Menet JS,Rosbash M

    更新日期:2011-09-02 00:00:00

  • Mechanism of foreign DNA selection in a bacterial adaptive immune system.

    abstract::In bacterial and archaeal CRISPR immune pathways, DNA sequences from invading bacteriophage or plasmids are integrated into CRISPR loci within the host genome, conferring immunity against subsequent infections. The ribonucleoprotein complex Cascade utilizes RNAs generated from these loci to target complementary "nonse...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.03.020

    authors: Sashital DG,Wiedenheft B,Doudna JA

    更新日期:2012-06-08 00:00:00

  • Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.

    abstract::The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00527-0

    authors: Li J,Williams BL,Haire LF,Goldberg M,Wilker E,Durocher D,Yaffe MB,Jackson SP,Smerdon SJ

    更新日期:2002-05-01 00:00:00

  • A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.

    abstract::The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor contro...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.08.013

    authors: He C,Hus JC,Sun LJ,Zhou P,Norman DP,Dötsch V,Wei H,Gross JD,Lane WS,Wagner G,Verdine GL

    更新日期:2005-10-07 00:00:00

  • R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters.

    abstract::R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-qua...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.10.008

    authors: Chen L,Chen JY,Zhang X,Gu Y,Xiao R,Shao C,Tang P,Qian H,Luo D,Li H,Zhou Y,Zhang DE,Fu XD

    更新日期:2017-11-16 00:00:00

  • Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast.

    abstract::Formation and maintenance of specialized plasma membrane domains are crucial for many biological processes, such as cell polarization and signaling. During isotropic bud growth, the yeast cell periphery is divided into two domains: the bud surface, an active site of exocytosis and growth, and the relatively quiescent ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80324-x

    authors: Barral Y,Mermall V,Mooseker MS,Snyder M

    更新日期:2000-05-01 00:00:00

  • Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes.

    abstract::Signals transmitted by ERK MAP kinases regulate the functions of multiple substrates present in the nucleus and in the cytoplasm. ERK signals are optimized by scaffold proteins that modulate their intensity and spatial fidelity. Once phosphorylated, ERKs dimerize, but how dimerization impacts on the activation of the ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.07.024

    authors: Casar B,Pinto A,Crespo P

    更新日期:2008-09-05 00:00:00

  • Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.

    abstract::Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encod...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.11.020

    authors: Raththagala M,Brewer MK,Parker MW,Sherwood AR,Wong BK,Hsu S,Bridges TM,Paasch BC,Hellman LM,Husodo S,Meekins DA,Taylor AO,Turner BD,Auger KD,Dukhande VV,Chakravarthy S,Sanz P,Woods VL Jr,Li S,Vander Kooi CW,Gentry

    更新日期:2015-01-22 00:00:00

  • SeqA blocking of DnaA-oriC interactions ensures staged assembly of the E. coli pre-RC.

    abstract::DnaA occupies only the three highest-affinity binding sites in E. coli oriC throughout most of the cell cycle. Immediately prior to initiation of chromosome replication, DnaA interacts with additional recognition sites, resulting in localized DNA-strand separation. These two DnaA-oriC complexes formed during the cell ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.09.016

    authors: Nievera C,Torgue JJ,Grimwade JE,Leonard AC

    更新日期:2006-11-17 00:00:00

  • A role for SIRT1 in the hypoxic response.

    abstract::In this issue of Molecular Cell, Lim et al. (2010) show that SIRT1 deacetylates HIF-1alpha and regulates its ability to respond to hypoxia, revealing yet another important function of SIRT1 and suggesting a connection between HIF function in aging and sirtuin enzymes. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2010.06.015

    authors: Leiser SF,Kaeberlein M

    更新日期:2010-06-25 00:00:00

  • Food for Growth: Distinct Nutrient Preferences between Primary Tumors and Metastases.

    abstract::In this issue of Molecular Cell, Rinaldi et al. (2021) reveal how nutrient availability in the metastatic niche of breast cancer cells shapes their growth signaling, highlighting potential avenues for therapeutic interventions. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2020.12.044

    authors: Audet-Delage Y,St-Pierre J

    更新日期:2021-01-21 00:00:00

  • The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability.

    abstract::SOCS3 is essential for regulating the extent, duration, and specificity of cellular responses to cytokines such as G-CSF and IL-6. Here we describe the solution structure of SOCS3, the first structure determined for any SOCS protein, in complex with a phosphotyrosine-containing peptide from the IL-6 receptor signaling...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.03.024

    authors: Babon JJ,McManus EJ,Yao S,DeSouza DP,Mielke LA,Sprigg NS,Willson TA,Hilton DJ,Nicola NA,Baca M,Nicholson SE,Norton RS

    更新日期:2006-04-21 00:00:00

  • Distressing bacteria: structure of a prokaryotic detox program.

    abstract::MazF and MazE are components of a chromosomal toxin-antitoxin system of Escherichia coli. In this issue of Molecular Cell, Kamada et al. describe the crystal structure of a MazE/MazF heterohexamer and propose that the mechanism of toxin-antidote recognition is common to other homologous chromosomal and plasmid-borne s...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/s1097-2765(03)00146-1

    authors: de la Cueva-Méndez G

    更新日期:2003-04-01 00:00:00

  • How Rho exerts its muscle on RNA.

    abstract::Rho factor in bacteria terminates transcription by using energy from ATP hydrolysis to forcefully dissociate the transcripts from RNA polymerase. used data from presteady-state ATPase kinetics to support a rational mechanistic model for Rho's action on RNA. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.molcel.2006.06.002

    authors: Richardson JP

    更新日期:2006-06-23 00:00:00