Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases.

Abstract:

:Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity. Acetylation site substitutions reduced p53-dependent transcriptional induction and G1 cell cycle arrest. Chromatin immunoprecipitation analysis of the endogenous p21 promoter showed increased association of p53, coactivators (CBP and TRRAP), and acetylated histones following cell irradiation. Results with acetylation-defective p53 demonstrate that the critical function of acetylation is not to increase the DNA binding affinity of p53 but rather to promote coactivator recruitment and histone acetylation. Therefore, we propose that an acetylation cascade consisting of p53 acetylation-dependent recruitment of coactivators/HATs is crucial for p53 function.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Barlev NA,Liu L,Chehab NH,Mansfield K,Harris KG,Halazonetis TD,Berger SL

doi

10.1016/s1097-2765(01)00414-2

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

1243-54

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(01)00414-2

journal_volume

8

pub_type

杂志文章
  • A pathway of sequential arginine-serine-rich domain-splicing signal interactions during mammalian spliceosome assembly.

    abstract::Serine-arginine (SR) proteins are general splicing factors and can function through binding to exonic splicing enhancers (ESEs). SR proteins and several other mammalian splicing factors contain an arginine-serine-rich (RS) domain required to promote splicing. We have recently found that the ESE bound RS domain functio...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.10.021

    authors: Shen H,Green MR

    更新日期:2004-11-05 00:00:00

  • Regulation of DNA Translocation Efficiency within the Chromatin Remodeler RSC/Sth1 Potentiates Nucleosome Sliding and Ejection.

    abstract::The RSC chromatin remodeler slides and ejects nucleosomes, utilizing a catalytic subunit (Sth1) with DNA translocation activity, which can pump DNA around the nucleosome. A central question is whether and how DNA translocation is regulated to achieve sliding versus ejection. Here, we report the regulation of DNA trans...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.03.032

    authors: Clapier CR,Kasten MM,Parnell TJ,Viswanathan R,Szerlong H,Sirinakis G,Zhang Y,Cairns BR

    更新日期:2016-05-05 00:00:00

  • Emerging Principles of Gene Expression Programs and Their Regulation.

    abstract::Many mechanisms contribute to regulation of gene expression to ensure coordinated cellular behaviors and fate decisions. Transcriptional responses to external signals can consist of many hundreds of genes that can be parsed into different categories based on kinetics of induction, cell-type and signal specificity, and...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2018.07.017

    authors: Pope SD,Medzhitov R

    更新日期:2018-08-02 00:00:00

  • A 3' exonuclease that specifically interacts with the 3' end of histone mRNA.

    abstract::Metazoan histone mRNAs end in a highly conserved stem-loop structure followed by ACCCA. Previous studies have suggested that the stem-loop binding protein (SLBP) is the only protein binding this region. Using RNA affinity purification, we identified a second protein, designated 3'hExo, that contains a SAP and a 3' exo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00278-8

    authors: Dominski Z,Yang XC,Kaygun H,Dadlez M,Marzluff WF

    更新日期:2003-08-01 00:00:00

  • Unlocking the proteasome door.

    abstract::How proteasomal ATPases stimulate the gate opening of 20S proteasomes is a longstanding question. In the September 7 issue of Molecular Cell, Smith et al. (2007) describe the conserved "HbYX" motif as the key to proteasome gate opening. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2007.09.001

    authors: Saeki Y,Tanaka K

    更新日期:2007-09-21 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

  • 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

  • A Eukaryotic Sensor for Membrane Lipid Saturation.

    abstract::Maintaining a fluid bilayer is essential for cell signaling and survival. Lipid saturation is a key factor determining lipid packing and membrane fluidity, and it must be tightly controlled to guarantee organelle function and identity. A dedicated eukaryotic mechanism of lipid saturation sensing, however, remains elus...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.05.015

    authors: Covino R,Ballweg S,Stordeur C,Michaelis JB,Puth K,Wernig F,Bahrami A,Ernst AM,Hummer G,Ernst R

    更新日期:2016-07-07 00:00:00

  • SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.

    abstract::Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80133-1

    authors: Desterro JM,Rodriguez MS,Hay RT

    更新日期:1998-08-01 00:00:00

  • Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis.

    abstract::The double Holliday junction (dHJ) is generally regarded to be a key intermediate of meiotic recombination, whose resolution is critical for the formation of crossover recombinants. In fission yeast, the Mus81-Eme1 endonuclease has been implicated in resolving dHJs. Consistent with this role, we show that Mus81-Eme1 i...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00343-5

    authors: Osman F,Dixon J,Doe CL,Whitby MC

    更新日期:2003-09-01 00:00:00

  • Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP turnover and dissociation of Rad51 from DNA.

    abstract::Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks and the generation of genetic diversity by homologous recombination (HR). In the presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded DNA to catalyze strand exchange. Inappropriate HR causes genomic instabilit...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.05.026

    authors: Antony E,Tomko EJ,Xiao Q,Krejci L,Lohman TM,Ellenberger T

    更新日期:2009-07-10 00:00:00

  • RNA polymerase I contains a TFIIF-related DNA-binding subcomplex.

    abstract::The eukaryotic RNA polymerases Pol I, II, and III use different promoters to transcribe different classes of genes. Promoter usage relies on initiation factors, including TFIIF and TFIIE, in the case of Pol II. Here, we show that the Pol I-specific subunits A49 and A34.5 form a subcomplex that binds DNA and is related...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.07.028

    authors: Geiger SR,Lorenzen K,Schreieck A,Hanecker P,Kostrewa D,Heck AJ,Cramer P

    更新日期:2010-08-27 00:00:00

  • UneCLIPsing HuR nuclear function.

    abstract::The RNA-binding protein HuR, while known to stabilize cytoplasmic mRNAs, is largely nuclear. In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2011.07.016

    authors: Srikantan S,Gorospe M

    更新日期:2011-08-05 00:00:00

  • Smad about E2F. TGFbeta repressionof c-Myc via a Smad3/E2F/p107 complex.

    abstract::Signaling by TGFbeta regulates the expression of hundreds of genes. The rapid repression of c-Myc stands out because of its roles in growth control and cancer. Recent work shows that c-Myc repression by TGFbeta is mediated by the nuclear translocation of a novel, preformed complex composed of Smad3, E2F4 or E2F5, and ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00584-1

    authors: Kowalik TF

    更新日期:2002-07-01 00:00:00

  • A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.

    abstract::FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00353-7

    authors: Rocchi S,Picard F,Vamecq J,Gelman L,Potier N,Zeyer D,Dubuquoy L,Bac P,Champy MF,Plunket KD,Leesnitzer LM,Blanchard SG,Desreumaux P,Moras D,Renaud JP,Auwerx J

    更新日期:2001-10-01 00:00:00

  • Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions.

    abstract::Death-fold domains constitute an evolutionarily conserved superfamily that mediates apoptotic signaling. These motifs, including CARD (caspase recruitment domain), DD (death domain), and DED (death effector domain), are believed to exert their effects solely through homotypic interactions. Herein we demonstrate that t...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.08.020

    authors: Nam YJ,Mani K,Ashton AW,Peng CF,Krishnamurthy B,Hayakawa Y,Lee P,Korsmeyer SJ,Kitsis RN

    更新日期:2004-09-24 00:00:00

  • MicroRNA pathways modulate polyglutamine-induced neurodegeneration.

    abstract::Nine human neurodegenerative diseases are due to expansion of a CAG repeat- encoding glutamine within the open reading frame of the respective genes. Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell death durin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.07.030

    authors: Bilen J,Liu N,Burnett BG,Pittman RN,Bonini NM

    更新日期:2006-10-06 00:00:00

  • pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities.

    abstract::The interaction between pRB and E2F is critical for control of the cell cycle and apoptosis. Here we report that pRB contains two distinct E2F binding sites. The previously identified E2F binding site on pRB is necessary for stable association with E2Fs on DNA. A second E2F interaction site is located entirely within ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00344-7

    authors: Dick FA,Dyson N

    更新日期:2003-09-01 00:00:00

  • Homeodomain position 54 specifies transcriptional versus translational control by Bicoid.

    abstract::Bicoid (BCD), the anterior determinant of Drosophila, controls embryonic gene expression by transcriptional activation and translational repression. Both functions require the homeodomain (HD), which recognizes DNA motifs at target gene enhancers and a specific sequence interval in the 3' untranslated region of caudal...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80434-7

    authors: Niessing D,Driever W,Sprenger F,Taubert H,Jäckle H,Rivera-Pomar R

    更新日期:2000-02-01 00:00:00

  • Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability.

    abstract::R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability; however, the mechanisms under...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.10.020

    authors: Sollier J,Stork CT,García-Rubio ML,Paulsen RD,Aguilera A,Cimprich KA

    更新日期:2014-12-18 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

  • A viral mechanism for remodeling chromatin structure in G0 cells.

    abstract::Small DNA viruses force quiescent cells to reenter the cell cycle in order to replicate their DNA. We report here that the adenovirus E1A protein creates an S phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-targeted genes. These genes are surrounded by Lys-9-methylated H3 histones,...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00225-9

    authors: Ghosh MK,Harter ML

    更新日期:2003-07-01 00:00:00

  • Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation.

    abstract::Solving the biological roles of covalent histone modifications, including monoubiquitination of histone H2A, and the molecular mechanisms by which these modifications regulate specific transcriptional programs remains a central question for all eukaryotes. Here we report that the N-CoR/HDAC1/3 complex specifically rec...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.11.002

    authors: Zhou W,Zhu P,Wang J,Pascual G,Ohgi KA,Lozach J,Glass CK,Rosenfeld MG

    更新日期:2008-01-18 00:00:00

  • Mind the Gapmer: Implications of Co-transcriptional Cleavage by Antisense Oligonucleotides.

    abstract::While gapmers efficiently knock down as well as terminate transcription of nascent lncRNAs and mRNAs, Lee and Mendell (2020) and Lai et al. (2020) also demonstrate that Pol II termination is not observed with gapmers targeting the 3' terminal portions of the transcript. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2020.02.010

    authors: Maranon DG,Wilusz J

    更新日期:2020-03-05 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

  • BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair.

    abstract::The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of tr...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.01.011

    authors: Hatchi E,Skourti-Stathaki K,Ventz S,Pinello L,Yen A,Kamieniarz-Gdula K,Dimitrov S,Pathania S,McKinney KM,Eaton ML,Kellis M,Hill SJ,Parmigiani G,Proudfoot NJ,Livingston DM

    更新日期:2015-02-19 00:00:00

  • DNA binding and bending to initiate packaging of phage lambda DNA.

    abstract::Physical and genetic studies verify that the DNA binding domain of protein gpNu1 (which initiates packaging of phage lambda DNA) is a winged helix-turn-helix (w HTH) and that gpNu1 dimers bind sites that are brought close through DNA bending. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/s1097-2765(02)00536-1

    authors: Campbell A

    更新日期:2002-05-01 00:00:00

  • Control of actin turnover by a salmonella invasion protein.

    abstract::Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(04)00053-x

    authors: McGhie EJ,Hayward RD,Koronakis V

    更新日期:2004-02-27 00:00:00

  • GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus.

    abstract::Transcriptional coregulators, rather than ligand signals, are suspected to confer context and pathway specificity to nuclear receptor signaling, but the identity of such specifying coregulators and the underlying molecular mechanisms remain largely enigmatic. Here we address this issue in metabolic oxysterol receptor ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.05.006

    authors: Jakobsson T,Venteclef N,Toresson G,Damdimopoulos AE,Ehrlund A,Lou X,Sanyal S,Steffensen KR,Gustafsson JA,Treuter E

    更新日期:2009-05-14 00:00:00

  • The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island Methylator phenotype.

    abstract::Most colorectal cancers (CRCs) containing activated BRAF (BRAF[V600E]) have a CpG island methylator phenotype (CIMP) characterized by aberrant hypermethylation of many genes, including the mismatch repair gene MLH1. MLH1 silencing results in microsatellite instability and a hypermutable phenotype. Through an RNAi scre...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.08.010

    authors: Fang M,Ou J,Hutchinson L,Green MR

    更新日期:2014-09-18 00:00:00