BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease.

Abstract:

:Amyloid beta (Aβ) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aβ production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aβ production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.

authors

Bao J,Qin M,Mahaman YAR,Zhang B,Huang F,Zeng K,Xia Y,Ke D,Wang Q,Liu R,Wang JZ,Ye K,Wang X

doi

10.1073/pnas.1800498115

subject

Has Abstract

pub_date

2018-04-10 00:00:00

pages

3954-3959

issue

15

eissn

0027-8424

issn

1091-6490

pii

1800498115

journal_volume

115

pub_type

杂志文章
  • High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine.

    abstract::Unlike normal cells, malignant rat and two simian virus 40-transformed human cell lines can neither grow nor survive in B12-and folate-supplemented media in which methionine is replaced by homocysteine. Yet three lines of evidence indicate that the malignant and transformed cells synthesize large amounts of methionine...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.5.1523

    authors: Hoffman RM,Erbe RW

    更新日期:1976-05-01 00:00:00

  • A channeled tRNA cycle during mammalian protein synthesis.

    abstract::In earlier studies it was shown that the mammalian translation system is highly organized in vivo and that the intermediates in the process, aminoacyl-tRNAs, are channeled--i.e., they are directly transferred from the aminoacyl-tRNA synthetases to the elongation factor to the ribosomes without dissociating into the ce...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.16.7158

    authors: Stapulionis R,Deutscher MP

    更新日期:1995-08-01 00:00:00

  • Hydrogen peroxide production, chemiluminescence, and the respiratory burst of fertilization: interrelated events in early sea urchin development.

    abstract::After fertilization of the sea urchin, Strongyl-ocentrotus purpuratus, a crosslinked fertilization membrane is formed; the crosslinks (dityrosine residues) are synthesized in a reaction catalyzed by an ovoperoxidase that is released from the cortical granules during fertilization. The substrate for ovoperoxidase activ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.7.3183

    authors: Foerder CA,Klebanoff SJ,Shapiro BM

    更新日期:1978-07-01 00:00:00

  • The maize transposable element system Ac/Ds as a mutagen in Arabidopsis: identification of an albino mutation induced by Ds insertion.

    abstract::A two-component transposon system based on the Ac element of maize was used as a mutagen in Arabidopsis thaliana. Transposition of a Ds element marked with a hygromycin-resistance gene was activated from four different locations in the Arabidopsis genome. The progeny of 201 plants carrying independent transposition ev...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.21.10370

    authors: Long D,Martin M,Sundberg E,Swinburne J,Puangsomlee P,Coupland G

    更新日期:1993-11-01 00:00:00

  • Task-related "cortical" bursting depends critically on basal ganglia input and is linked to vocal plasticity.

    abstract::Basal ganglia-thalamocortical circuits are critical for motor control and motor learning. Classically, basal ganglia nuclei are thought to regulate motor behavior by increasing or decreasing cortical firing rates, and basal ganglia diseases are assumed to reflect abnormal overall activity levels. More recent studies s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1216308110

    authors: Kojima S,Kao MH,Doupe AJ

    更新日期:2013-03-19 00:00:00

  • Rational design of a triple helix-specific intercalating ligand.

    abstract::DNA triple helices offer new perspectives toward oligonucleotide-directed gene regulation. However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. Molecular modeling and thermal denaturati...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.7.3591

    authors: Escudé C,Nguyen CH,Kukreti S,Janin Y,Sun JS,Bisagni E,Garestier T,Hélène C

    更新日期:1998-03-31 00:00:00

  • Partial purification and characterization of DNA from the human X chromosome.

    abstract::Human X chromosome DNA was partially purified from a mouse-human hybrid cell line containing a single human chromosome, the X. Enrichment of such DNA was accomplished by two sequential reassociations of radiolabeled hybrid cell DNA with large excesses of mouse DNA. Unreassociated hybrid cell DNA was used as a probe fo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.12.6525

    authors: Schmeckpeper BJ,Smith KD,Dorman BP,Ruddle FH,Talbot CC Jr

    更新日期:1979-12-01 00:00:00

  • Mating signal and DNA penetration deficiency in conjugation between male Escherichia coli and minicells.

    abstract::Strain OU122, a dnaB mutant of HfrH which stops vegetative DNA synthesis immediately when the temperature is shifted to 43 degrees, was mated at 43 degrees with minicells with and without 1 mM Zn2+. Synthesis of DNA was detected in the mating mixture containing minicells derived from either Fchi925 or F+chi115 cells, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.9.3721

    authors: Ou JT

    更新日期:1975-09-01 00:00:00

  • The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide.

    abstract::Solution at 2.5-A resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (beta2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with beta2m,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.13.6880

    authors: Balendiran GK,Solheim JC,Young AC,Hansen TH,Nathenson SG,Sacchettini JC

    更新日期:1997-06-24 00:00:00

  • An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node.

    abstract::Voltage-gated Na(+) channels are composed of pore-forming alpha and auxiliary beta subunits. The majority of Na(+) channels in the heart contain tetrodotoxin (TTX)-insensitive Na(v)1.5 alpha subunits, but TTX-sensitive brain-type Na(+) channel alpha subunits are present and functionally important in the transverse tub...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2627986100

    authors: Maier SK,Westenbroek RE,Yamanushi TT,Dobrzynski H,Boyett MR,Catterall WA,Scheuer T

    更新日期:2003-03-18 00:00:00

  • Spatial restriction of receptor tyrosine kinase activity through a polarized endocytic cycle controls border cell migration.

    abstract::Border cell migration is a stereotyped migration occurring during the development of the Drosophila egg chamber. During this process, a cluster composed of six to eight follicle cells migrates between nurse cells toward the oocyte. Receptor tyrosine kinases (RTKs) are enriched at the leading edge of the follicle cells...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1010795108

    authors: Assaker G,Ramel D,Wculek SK,González-Gaitán M,Emery G

    更新日期:2010-12-28 00:00:00

  • Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice.

    abstract::Compulsive behavior is a debilitating clinical feature of many forms of neuropsychiatric disease, including Tourette syndrome, obsessive-compulsive spectrum disorders, eating disorders, and autism. Although several studies link striatal dysfunction to compulsivity, the pathophysiology remains poorly understood. Here, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1308195110

    authors: Xu P,Grueter BA,Britt JK,McDaniel L,Huntington PJ,Hodge R,Tran S,Mason BL,Lee C,Vong L,Lowell BB,Malenka RC,Lutter M,Pieper AA

    更新日期:2013-06-25 00:00:00

  • Responses of hair follicle-associated structures to loss of planar cell polarity signaling.

    abstract::The mammalian hair follicle unit consists of a central follicle and a series of associated structures: sebaceous glands, arrector pili muscles, Merkel cells, and sensory nerve endings. The architecture of this multicellular structure is highly polarized with respect to the body axes. Previous work has implicated Frizz...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1301430110

    authors: Chang H,Nathans J

    更新日期:2013-03-05 00:00:00

  • Orientation selectivity and noise correlation in awake monkey area V1 are modulated by the gamma cycle.

    abstract::Gamma-band synchronization adjusts the timing of excitatory and inhibitory inputs to a neuron. Neurons in the visual cortex are selective for stimulus orientation because of dynamic interactions between excitatory and inhibitory inputs. We hypothesized that these interactions and hence also orientation selectivity var...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114223109

    authors: Womelsdorf T,Lima B,Vinck M,Oostenveld R,Singer W,Neuenschwander S,Fries P

    更新日期:2012-03-13 00:00:00

  • Inactivation of DNA proofreading obviates the need for SOS induction in frameshift mutagenesis.

    abstract::Translesion synthesis at replication-blocking lesions requires the induction of proteins that are controlled by the SOS system in Escherichia coli. Of the proteins identified so far, UmuD', UmuC, and RecA* were shown to facilitate replication across UV-light-induced lesions, yielding both error-free and mutagenic tran...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.13114

    authors: Fuchs RP,Napolitano RL

    更新日期:1998-10-27 00:00:00

  • Most invasive species largely conserve their climatic niche.

    abstract::The ecological niche is a key concept for elucidating patterns of species distributions and developing strategies for conserving biodiversity. However, recent times are seeing a widespread debate whether species niches are conserved across space and time (niche conservatism hypothesis). Biological invasions represent ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2004289117

    authors: Liu C,Wolter C,Xian W,Jeschke JM

    更新日期:2020-09-22 00:00:00

  • Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis.

    abstract::The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2003524117

    authors: Beesley S,Kim DW,D'Alessandro M,Jin Y,Lee K,Joo H,Young Y,Tomko RJ Jr,Faulkner J,Gamsby J,Kim JK,Lee C

    更新日期:2020-11-10 00:00:00

  • Antioxidants prevent health-promoting effects of physical exercise in humans.

    abstract::Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unkn...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903485106

    authors: Ristow M,Zarse K,Oberbach A,Klöting N,Birringer M,Kiehntopf M,Stumvoll M,Kahn CR,Blüher M

    更新日期:2009-05-26 00:00:00

  • Mitogenic leukoagglutinin from Phaseolus vulgaris binds to a pentasaccharide unit in N-acetyllactosamine-type glycoprotein glycans.

    abstract::The carbohydrate binding specificity of leukoagglutinin (La; Phaseolus vulgaris isolectin L4) was studied by using quantitative precipitation and precipitation-inhibition. A series of purified glycopeptides and synthetic oligosaccharides were used as inhibitors. The minimal structural unit required for La binding was ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.5.1611

    authors: Hammarström S,Hammarström ML,Sundblad G,Arnarp J,Lönngren J

    更新日期:1982-03-01 00:00:00

  • MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins.

    abstract::p300 acetylates and activates the tumor suppressor p53 after DNA damage. Here, we show that MDM2, a negative-feedback regulator of p53, inhibited p300-mediated p53 acetylation by complexing with these two proteins. First, we purified a p300-MDM2-p53 protein complex from HeLa nuclear extracts, which was inactive in p53...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.23.12547

    authors: Kobet E,Zeng X,Zhu Y,Keller D,Lu H

    更新日期:2000-11-07 00:00:00

  • Nitrate storage and retrieval in Beta vulgaris: Effects of nitrate and chloride on proton gradients in tonoplast vesicles.

    abstract::The fluorescent probes acridine orange and oxonol-V were used as indicators of pH gradients (DeltapH) and membrane potential differences (DeltaPsi), respectively, in membrane vesicles believed to be derived from the tonoplast of Beta vulgaris L. Low concentrations of nitrate (1-5 mM) caused a partial dissipation of bo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.11.3683

    authors: Blumwald E,Poole RJ

    更新日期:1985-06-01 00:00:00

  • Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine.

    abstract::In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0705346104

    authors: Marutle A,Ohmitsu M,Nilbratt M,Greig NH,Nordberg A,Sugaya K

    更新日期:2007-07-24 00:00:00

  • Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer.

    abstract::Src tyrosine kinase has long been implicated in colon cancer but much remains to be learned about its substrates. The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) has just recently been implicated in colon cancer but its role is poorly defined. Here we show that c-Src phosphorylates human HNF4α on three tyros...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1106799109

    authors: Chellappa K,Jankova L,Schnabl JM,Pan S,Brelivet Y,Fung CL,Chan C,Dent OF,Clarke SJ,Robertson GR,Sladek FM

    更新日期:2012-02-14 00:00:00

  • In vitro synthesis of RNA that contains polyadenylate by virion-associated RNA polymerase of vesicular stomatitis virus.

    abstract::The RNA synthesized in vitro by the virion-associated RNA-instructed RNA polymerase of purified vesicular stomatitis virus contains polyadenylate sequences. These have been demonstrated by their partial resistance to pancreatic and T(1) ribonucleases and their capacity to bind to poly(U) filters and oligo(dT)-cellulos...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.12.3566

    authors: Banerjee AK,Rhodes DP

    更新日期:1973-12-01 00:00:00

  • Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease.

    abstract::Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients wit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1408523111

    authors: Payne F,Lim K,Girousse A,Brown RJ,Kory N,Robbins A,Xue Y,Sleigh A,Cochran E,Adams C,Dev Borman A,Russel-Jones D,Gorden P,Semple RK,Saudek V,O'Rahilly S,Walther TC,Barroso I,Savage DB

    更新日期:2014-06-17 00:00:00

  • On the stereochemistry and biosynthesis of lipoxin B.

    abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.7.1983

    authors: Serhan CN,Hamberg M,Samuelsson B,Morris J,Wishka DG

    更新日期:1986-04-01 00:00:00

  • Association of mitochondria with microtubules in cultured cells.

    abstract::By indirect immunofluorescence techniques, microtubules and mitochondria were localized in normal rat kidney cells, human WI38 fibroblasts, mouse peritoneal macrophages, and a putative smooth muscle rat cell line, in monolayer culture. The mitochondria were found to be arranged along the cytoplasmic microtubules in ea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.8.3863

    authors: Heggeness MH,Simon M,Singer SJ

    更新日期:1978-08-01 00:00:00

  • The endoplasmic reticulum: a cytochemist's view (a review).

    abstract::Enzyme cytochemistry has been used, at the light and electron microscope levels, to "mark" cytoplasmic organelles of mammalian cells. Catalase cytochemistry permitted identification of microperoxisomes, apparently ubiquitous organelles that are attached by numerous slender connections to the endoplasmic reticulum. Thi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.73.8.2781

    authors: Novikoff AB

    更新日期:1976-08-01 00:00:00

  • Humans quickly learn to blink strategically in response to environmental task demands.

    abstract::Eye blinking is one of the most frequent human actions. The control of blinking is thought to reflect complex interactions between maintaining clear and healthy vision and influences tied to central dopaminergic functions including cognitive states, psychological factors, and medical conditions. The most imminent cons...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1714220115

    authors: Hoppe D,Helfmann S,Rothkopf CA

    更新日期:2018-02-27 00:00:00

  • Evidence for procollagen, a biosynthetic precursors of collagen.

    abstract::Incubation of rat calvaria for short times in the presence of a labeled amino acid revealed the existence of a collagen fraction (procollagen) that functions as a biosynthetic precursor of collagen. Procollagen contains an alpha1-like chain (pre-alpha1) that elutes earlier from CM-cellulose than does rat-bone alpha1 a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.6.1138

    authors: Bellamy G,Bornstein P

    更新日期:1971-06-01 00:00:00