Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation

Jiang, Yong-hui; Armstrong, Dawna; Albrecht, Urs; Atkins, Coleen M; Noebels, Jeffrey L; Eichele, Gregor; Sweatt, J.David; Beaudet, Arthur L

doi:10.1016/s0896-6273(00)80596-6

Cited by 852Genetic Syndromes and ImprintingGenetics and Neurodevelopmental DisordersUbiquitin and proteasome pathways

Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation

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Jiang, Yong-hui, Armstrong, Dawna, Albrecht, Urs, Atkins, Coleen M, Noebels, Jeffrey L, Eichele, Gregor, Sweatt, J.David, Beaudet, Arthur L·1998·Neuron

DOI 10.1016/s0896-6273(00)80596-6

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Abstract

The E6-AP ubiquitin ligase (human/mouse gene UBE3A/Ube3a) promotes the degradation of p53 in association with papilloma E6 protein, and maternal deficiency causes human Angelman syndrome (AS). Ube3a is imprinted with silencing of the paternal allele in hippocampus and cerebellum in mice. We found that the phenotype of mice with maternal deficiency (m-/p+) for Ube3a resembles human AS with motor dysfunction, inducible seizures, and a context-dependent learning deficit. Long-term potentiation (LTP) was severely impaired in m-/p+ mice despite normal baseline synaptic transmission and neuroanatomy, indicating that ubiquitination may play a role in mammalian LTP and that LTP may be abnormal in AS. The cytoplasmic abundance of p53 was increased in postmitotic neurons in m-/p+ mice and in AS, providing a potential biochemical basis for the phenotype through failure to ubiquitinate and degrade various effectors.

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Mice with a deletion in the maternal copy of Ube3A have impairments in learning and in the LTP form of synaptic plasticity.
“Mice that carry a deletion in the maternal copy of Ube3A have impairments in learning and in the LTP form of synaptic plasticity90.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [90]
Ube3a protein regulates excitatory-inhibitory balance during brain development, and when its expression is perturbed ASD may occur.
“These studies suggest that Ube3a protein regulates excitatory–inhibitory balance during brain development and that when the level of expression is perturbed ASD may occur.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [90]
In a mouse model with maternal Ube3a deleted (Ube3am−/p+), total brain weight and cortex and cerebellum weights are lower than in wild-type.
“Similar to the observation of small brain size in human samples from Angelman’s syndrome, the total brain weight, as well as the weight of the cortex and cerebellum, is lower in a mouse model with maternal Ube3a deleted (Ube3am−/p+) [181].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [181]

Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 1× · see citing works
“The p53 protein is also subjectparticularly appealing prospect in the case of PKC, where proteolytically activated forms of the kinase have to ubiquitination by MDM2, another E3 ubiquitin ligase (Haupt et al., 1997; Kubbutat et al., 1997).”
Background
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Modality-Specific Retrograde Amnesia of Fear
Kim, J. J., & Fanselow, M. S. (1992) · Science · doi:10.1126/science.1585183 · Cited by 2,483 · see citing works
p53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,338 · see citing works
UBIQUITIN-DEPENDENT PROTEIN DEGRADATION
Hochstrasser, M. (1996) · Annual Review of Genetics · doi:10.1146/annurev.genet.30.1.405 · Cited by 1,695 · see citing works
The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2’s inhibition of p53
Pomerantz, J., Schreiber-Agus, N., Liégeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.-W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81400-2 · Cited by 1,521 · see citing works
The Proteasome: Paradigm of a Self-Compartmentalizing Protease
Baumeister, W. P., Walz, J., Zühl, F., & Seemüller, E. (1998) · Cell · doi:10.1016/s0092-8674(00)80929-0 · Cited by 1,497 · see citing works
UBE3A/E6-AP mutations cause Angelman syndrome
Kishino, T., Lalande, M., & Wagstaff, J. E. (1997) · Nature Genetics · doi:10.1038/ng0197-70 · Cited by 1,304 · see citing works
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
Barria, A., Muller, D., Derkach, V., Griffith, L. C., & Soderling, T. R. (1997) · Science · doi:10.1126/science.276.5321.2042 · Cited by 1,049 · see citing works
Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascade
Scheffner, M., Nuber, U. A., & Huibregtse, J. M. (1995) · Nature · doi:10.1038/373081a0 · Cited by 1,017 · see citing works
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
Huibregtse, J. M., Scheffner, M., Beaudenon, S. L., & Howley, P. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.2563 · Cited by 1,011 · see citing works
Site-Specific Phosphorylation of IκBα by a Novel Ubiquitination-Dependent Protein Kinase Activity
Chen, Z. J., Parent, L. A., & Maniatis, T. (1996) · Cell · doi:10.1016/s0092-8674(00)81064-8 · Cited by 958 · see citing works
A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18.
Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04990.x · Cited by 879 · see citing works
De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome
Matsuura, T., Sutcliffe, J. S., Fang, P., Galjaard, R. H., Jiang, Y., Benton, C. S., Rommens, J. M., & Beaudet, A. L. (1997) · Nature Genetics · doi:10.1038/ng0197-74 · Cited by 858 · see citing works
Self-citation
Ubiquitination of a Yeast Plasma Membrane Receptor Signals Its Ligand-Stimulated Endocytosis
Hicke, L., & Riezman, H. (1996) · Cell · doi:10.1016/s0092-8674(00)80982-4 · Cited by 783 · see citing works
GENOMIC IMPRINTING IN MAMMALS
Bartolomei, M. S., & Tilghman, S. M. (1997) · Annual Review of Genetics · doi:10.1146/annurev.genet.31.1.493 · Cited by 632 · see citing works
Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear.
Kim, J. J., Rison, R. A., & Fanselow, M. S. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.6.1093 · Cited by 615 · see citing works
Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15
Buiting, K., Saitoh, S., Groß, S., Dittrich, B., Schwartz, S., Nicholls, R. D., & Horsthemke, B. (1995) · Nature Genetics · doi:10.1038/ng0495-395 · Cited by 595 · see citing works
Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons
Albrecht, U., Sutcliffe, J. S., Cattanach, B. M., BEECHEY, C. V., Armstrong, D. L., Gregor Eichele, C., & Beaudet, A. L. (1997) · Nature Genetics · doi:10.1038/ng0997-75 · Cited by 586 · see citing works
Self-citation
Cloning and Expression of the cDNA for E6-AP, a Protein that Mediates the Interaction of the Human Papillomavirus E6 Oncoprotein with p53
Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.775 · Cited by 553 · see citing works
The ubiquitin-proteasome pathway: The complexity and myriad functions of proteins death
Ciechanover, A. J., & Schwartz, A. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2727 · Cited by 509 · see citing works
Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation.
Sacktor, T. C., Osten, P., Valsamis, H. A., Jiang, X., Naik, M. U., & Sublette, M. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8342 · Cited by 450 · see citing works
The Angelman syndrome candidate gene, UBE3AIE6-AP, is imprinted in brain
Rougeulle, C., Glatt, H., & Lalande, M. (1997) · Nature Genetics · doi:10.1038/ng0997-14 · Cited by 416 · see citing works
Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region
Sutcliffe, J. S., Nakao, M., Christian, S. L., Ørstavik, K. H., Tommerup, N., Ledbetter, D. H., & Beaudet, A. L. (1994) · Nature Genetics · doi:10.1038/ng0994-52 · Cited by 413 · see citing works
Self-citation
Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.
Masutani, C., Sugasawa, K., Yanagisawa, J., Sonoyama, T., Ui, M., Enomoto, T., Takio, K., Tanaka, K., van der Spek, P. J., & Bootsma, D. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06452.x · Cited by 400 · see citing works
Long-term potentiation is associated with an increased activity of Ca2+/calmodulin-dependent protein kinase II.
Fukunaga, K., Stoppini, L., Miyamoto, E., & Muller, D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53037-4 · Cited by 398 · see citing works
Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice.
Bullard, D. C., Kunkel, E. J., Kubo, H., Hicks, J. M., Lorenzo, I., Doyle, N. A., Doerschuk, C. M., Ley, K. F., & Beaudet, A. L. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.5.2329 · Cited by 372 · see citing works
Self-citation
Ubiquitin C-Terminal Hydrolase Is an Immediate-Early Gene Essential for Long-Term Facilitation in Aplysia
Hegde, A. N., Inokuchi, K., Pei, W., Casadio, A., Ghirardi, M., Chain, D. G., Martin, K. C., Kandel, E. R., & Schwartz, J. H. (1997) · Cell · doi:10.1016/s0092-8674(00)80188-9 · Cited by 356 · see citing works
The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice
Perry, W. L., Hustad, C., Swing, D. A., O'Sullivan, T., Jenkins, N., & Copeland, N. (1998) · Nature Genetics · doi:10.1038/ng0298-143 · Cited by 354 · see citing works
Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain
Vu, T. H., & Hoffman, A. R. (1997) · Nature Genetics · doi:10.1038/ng0997-12 · Cited by 321 · see citing works
N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus.
Chetkovich, D. M., Gray, R., Johnston, D., & Sweatt, J. D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.15.6467 · Cited by 284 · see citing works
Self-citation
Evidence of Contextual Fear after Lesions of the Hippocampus: A Disruption of Freezing But Not Fear-Potentiated Startle
McNish, K. A., Gewirtz, J. C., & Davis, M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09353.1997 · Cited by 281 · see citing works
Protein Degradation or Regulation: Ub the Judge
Hochstrasser, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81058-2 · Cited by 280 · see citing works
Purkinje Cell Expression of a Mutant Allele ofSCA1in Transgenic Mice Leads to Disparate Effects on Motor Behaviors, Followed by a Progressive Cerebellar Dysfunction and Histological Alterations
Clark, H. B., Burright, E. N., Yunis, W. S., Larson, S., Wilcox, C., Hartman, B. K., Matilla‐Dueñas, A., Zoghbi, H. Y., & Orr, H. T. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-19-07385.1997 · Cited by 272 · see citing works
Mdm2: keeping p53 under control
Piette, J. G., Neel, H., & Maréchal, V. (1997) · Oncogene · doi:10.1038/sj.onc.1201432 · Cited by 268 · see citing works
The Role of E6AP in the Regulation of p53 Protein Levels in Human Papillomavirus (HPV)-positive and HPV-negative Cells
Talis, A. L., Huibregtse, J. M., & Howley, P. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6439 · Cited by 261 · see citing works
Mechanism of protein kinase C activation during the induction and maintenance of long-term potentiation probed using a selective peptide substrate.
Klann, E., Chen, S. J., & Sweatt, J. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8337 · Cited by 260 · see citing works
Self-citation
A novel intermediate stage in the transition between short- and long-term facilitation in the sensory to motor neuron synapse of aplysia
Ghirardi, M., Montarolo, P. G., & Kandel, E. R. (1995) · Neuron · doi:10.1016/0896-6273(95)90297-x · Cited by 198 · see citing works
Nuclear localization is essential for the activity of p53 protein.
Shaulsky, G., Goldfinger, N., Tosky, M. S., Levine, A. J., & Rotter, V. (1991) · PubMed · Cited by 192 · see citing works
Angelman syndrome: Correlations between epilepsy phenotypes and genotypes
Minassian, B. A., DeLorey, T. M., Olsen, R. W., Philippart, M., Bronstein, Y. L., Zhang, Q., Guerrini, R., Ness, P. V., Livet, M. O., & Delgado‐Escueta, A. V. (1998) · Annals of Neurology · doi:10.1002/ana.410430412 · Cited by 190 · see citing works
A Million Dollar Question: Does LTP = Memory?
Stevens, C. F. (1998) · Neuron · doi:10.1016/s0896-6273(00)80426-2 · Cited by 180 · see citing works
PARENTAL IMPRINTING AND HUMAN DISEASE
Lalande, M. (1996) · Annual Review of Genetics · doi:10.1146/annurev.genet.30.1.173 · Cited by 169 · see citing works
Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells.
Shaulsky, G., Ben‐Ze'ev, A., & Rotter, V. (1990) · PubMed · Cited by 168 · see citing works
Persistent protein kinase activation in the maintenance phase of long-term potentiation.
Klann, E., Chen, S. J., & Sweatt, J. D. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54221-6 · Cited by 165 · see citing works
Self-citation
Transient Activation of Cyclic AMP-dependent Protein Kinase during Hippocampal Long-term Potentiation
Roberson, E. D., & Sweatt, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.48.30436 · Cited by 160 · see citing works
Self-citation
Physical Interaction between Specific E2 and Hect E3 Enzymes Determines Functional Cooperativity
Kumar, S., Kao, W. H., & Howley, P. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13548 · Cited by 152 · see citing works
Genomic imprinting: potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes
Glenn, C. (1997) · Molecular Human Reproduction · doi:10.1093/molehr/3.4.321 · Cited by 145 · see citing works
Persistent and transcriptionally-dependent increase in protein phosphorylation in long-term facilitation ofAplysia sensory neurons
Sweatt, J. D., & Kandel, E. R. (1989) · Nature · doi:10.1038/339051a0 · Cited by 132 · see citing works
Self-citation
The HumanE6-APGene (UBE3A) Encodes Three Potential Protein Isoforms Generated by Differential Splicing
Yamamoto, Y., Huibregtse, J. M., & Howley, P. M. (1997) · Genomics · doi:10.1006/geno.1997.4617 · Cited by 128 · see citing works
Imprinting analysis of three genes in the Prader — Willi/Angelman region: SNRPN, E6-associated protein, and PAR-2 (D15S225E)
Nakao, M., Sutcliffe, J. S., Durtschl, B., Mutlrangura, A., Ledbetter, D. H., & Beaudet, A. L. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.2.309 · Cited by 122 · see citing works
Self-citation
Imprinting in Angelman and Prader-Willi syndromes
Jiang, Y.-H., Tsai, T., Bressler, J., & Beaudet, A. L. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80091-9 · Cited by 122 · see citing works
Self-citation
bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog
Oh, C., McMahon, R., Benzer, S., & Tanouye, M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-05-03166.1994 · Cited by 116 · see citing works
Antisense targeting of E6AP elevates p53 in HPV-infected cells but not in normal cells
Beer‐Romero, P., Glass, S., & Rolfe, M. (1997) · Oncogene · doi:10.1038/sj.onc.1200872 · Cited by 114 · see citing works
Puppet‐like syndrome of Angelman: A pathologic and neurochemical study
Jay, V., Becker, L. E., Chan, F.-W., & Perry, T. L. (1991) · Neurology · doi:10.1212/wnl.41.3.416 · Cited by 109 · see citing works
Molecular and clinical study of 61 Angelman syndrome patients
Saitoh, S., Harada, N., Jinno, Y., et al. (1994) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320520207 · Cited by 104 · see citing works
A candidate model for angelman syndrome in the mouse
Cattanach, B. M., Barr, J. A., BEECHEY, C. V., Martin, J. E., Noebels, J. L., & Jones, J. B. (1997) · Mammalian Genome · doi:10.1007/s003359900479 · Cited by 90 · see citing works
Self-citation
Subcellular Localization and Ubiquitin-conjugating Enzyme (E2) Interactions of Mammalian HECT Family Ubiquitin Protein Ligases
Hatakeyama, S., Jensen, J. P., & Weissman, A. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.24.15085 · Cited by 90 · see citing works
Persistent activation of cAMP-dependent protein kinase by regulated proteolysis suggests a neuron-specific function of the ubiquitin system in Aplysia
Chain, D. G., Hegde, A., Yamamoto, N., Liu-Marsh, B., & Schwartz, J. H. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-11-07592.1995 · Cited by 86 · see citing works
The 'happy puppet' syndrome of Angelman: review of the clinical features.
Robb, S. A., Pohl, K., Baraitser, M., Wilson, J., & Brett, E. M. (1989) · Archives of Disease in Childhood · doi:10.1136/adc.64.1.83 · Cited by 71 · see citing works
Angelman syndrome
Williams, C. A., Zori, R. T., Hendrickson, J., Stalker, H., Marum, T., Whidden, E. M., & Driscoll, D. J. (1995) · Current Problems in Pediatrics · doi:10.1016/s0045-9380(06)80036-8 · Cited by 66 · see citing works
Provirus integration into a gene encoding a ubiquitin-conjugating enzyme results in a placental defect and embryonic lethality.
Harbers, K., Müller, U., Grams, A. E., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12412 · Cited by 64 · see citing works
A regulatory subunit of the cAMP-dependent protein kinase down-regulated in aplysia sensory neurons during long-term sensitization
Bergold, P. J., Beushausen, S. A., Sacktor, T. C., Cheley, S., Bayley, H., & Schwartz, J. H. (1992) · Neuron · doi:10.1016/0896-6273(92)90304-v · Cited by 63 · see citing works
Fatal Convulsive Seizures in theDBAMouse Strain
Vicari, E. M. (1951) · The Journal of Psychology · doi:10.1080/00223980.1951.9916086 · Cited by 49 · see citing works
The Puppet-like Syndrome of Angelman
Dooley, J. M. (1981) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1981.02130310027010 · Cited by 38 · see citing works
Autonomously active protein kinase C in the maintenance phase of N-methyl-D-aspartate receptor-independent long term potentiation.
Powell, C. M., Johnston, D., & Sweatt, J. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)46880-9 · Cited by 32 · see citing works
Self-citation
Characterization of the interactions of human papillomavirus type 16 E6 with p53 and E6-associated protein in insect and human cells.
Daniels, P. R., Maitland, N. J., & Sanders, C. M. (1998) · Journal of General Virology · doi:10.1099/0022-1317-79-3-489 · Cited by 31 · see citing works
An essential ubiquitin‐conjugating enzyme with tissue and developmental specificity in th nematode Caenorhabditis elegans.
Zhen, M., Schein, J., Baillie, D. L., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00687.x · Cited by 27 · see citing works
Missense mutation R1066C in the second transmembrane domain of CFTR causes a severe cystic fibrosis phenotype: Study of 19 heterozygous and 2 homozygous patients
Casals, T., Pacheco, P. R., Barreto, C., Giménez, J., Ramos, M., Pereira, S., Pinheiro, J. A., Cobos, N., Curvelo, A., Vázquez, C., et al. (1997) · Human Mutation · doi:10.1002/(sici)1098-1004(1997)10:5 · Cited by 15 · see citing works

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Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system
Ehlers, M. D. (2003) · Nature Neuroscience · doi:10.1038/nn1013 · Cited by 977 · see citing works
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators
Smith, C. L., & O’Malley, B. W. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0023 · Cited by 931 · see citing works
Angelman syndrome: a review of the clinical and genetic aspects
Clayton-Smith, J., & Laan, L. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.2.87 · Cited by 687 · see citing works
Activity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666 · see citing works
The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc
Greer, P. L., Hanayama, R., Bloodgood, B. L., Mardinly, A. R., Lipton, D. M., Flavell, S. W., Kim, T.-K., Griffith, E. C., Waldon, Z., Maehr, R., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.026 · Cited by 30 · see citing works
Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning
Weeber, E. J., Beffert, U., Jones, C., Christian, J. M., Förster, E., Sweatt, J. D., & Herz, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205147200 · Cited by 623 · see citing works
Self-citation
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Nicholls, R. D., & Knepper, J. L. (2001) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.2.1.153 · Cited by 625 · see citing works
Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536 · see citing works
Ubiquitination Regulates PSD-95 Degradation and AMPA Receptor Surface Expression
Colledge, M., Snyder, E. M., Crozier, R. A., Soderling, J. A., Jin, Y., Langeberg, L. K., Lu, H., Bear, M. F., & Scott, J. D. (2003) · Neuron · doi:10.1016/s0896-6273(03)00687-1 · Cited by 567 · see citing works
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3
Wang, X., McCoy, P. A., Rodriguiz, R. M., Pan, Y., Je, H. S., Roberts, A. C., Kim, C. J., Berrios, J., Colvin, J. S., Bousquet-Moore, D., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr212 · Cited by 537 · see citing works
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Tai, H.-C., & Schuman, E. M. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2499 · Cited by 532 · see citing works
Neuronal Activity-Regulated Gene Transcription in Synapse Development and Cognitive Function
West, A. E., & Greenberg, M. E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005744 · Cited by 532 · see citing works
Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders
Lee, E., Lee, J., & Kim, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.011 · Cited by 468 · see citing works
Epigenetic mechanisms in cognition
Day, J. J., & Sweatt, J. D. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.019 · Cited by 510 · see citing works
Self-citation
Autism as a disorder of neural information processing: Directions for research and targets for therapy
Belmonte, M. K., Cook, E. H., Anderson, G. M., Rubenstein, J. L. R., Greenough, W. T., Beckel-Mitchener, A., Courchesne, E., Boulanger, L. M., Powell, S. B., Levitt, P. R., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001499 · Cited by 442 · see citing works
Self-citation
The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology
Dindot, S. V., Antalffy, B. A., Bhattacharjee, M. B., & Beaudet, A. L. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm288 · Cited by 418 · see citing works
Self-citation
Synaptic Protein Degradation Underlies Destabilization of Retrieved Fear Memory
Lee, S.-H., Choi, J.-H., Lee, N., Lee, H.-R., Kim, J.-I., Yu, N.-K., Choi, S.-L., Lee, S.-H., Kim, H., & Kaang, B.-K. (2008) · Science · doi:10.1126/science.1150541 · Cited by 409 · see citing works
Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
Huang, H.-S., Allen, J. A., Mabb, A. M., King, I. F., Miriyala, J., Taylor-Blake, B., Sciaky, N., Dutton, J. W., Lee, H.-M., Chen, X., et al. (2012) · Nature · doi:10.1038/nature10726 · Cited by 387 · see citing works
Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1
Lin, X., Antalffy, B., Kang, D., Orr, H. T., & Zoghbi, H. Y. (2000) · Nature Neuroscience · doi:10.1038/72101 · Cited by 374 · see citing works
Ube3a is required for experience-dependent maturation of the neocortex
Yashiro, K., Riday, T. T., Condon, K. H., Roberts, A. C., Bernardo, D. R., Prakash, R., Weinberg, R. J., Ehlers, M. D., & Philpot, B. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2327 · Cited by 328 · see citing works
Mechanisms of imprinting of the Prader-Willi/Angelman region
Horsthemke, B., & Wagstaff, J. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32364 · Cited by 320 · see citing works
The Emerging Field of Neuroepigenetics
Sweatt, J. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.023 · Cited by 324 · see citing works
Self-citation
Autism: A “Critical Period” Disorder?
LeBlanc, J. J., & Fagiolini, M. (2011) · Neural Plasticity · doi:10.1155/2011/921680 · Cited by 301 · see citing works
(Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features
Peier, A. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.8.1145 · Cited by 285 · see citing works
Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation
van Woerden, G. M., Harris, K. D., Hojjati, M. R., Gustin, R. M., Qiu, S., de Avila Freire, R., Jiang, Y.-H., Elgersma, Y., & Weeber, E. J. (2007) · Nature Neuroscience · doi:10.1038/nn1845 · Cited by 281 · see citing works
Self-citation
Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice
Smith, S. E. P., Zhou, Y.-D., Zhang, G., Jin, Z., Stoppel, D. C., & Anderson, M. P. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002627 · Cited by 267 · see citing works
Deconstruction for Reconstruction: The Role of Proteolysis in Neural Plasticity and Disease
Bingol, B., & Sheng, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.11.006 · Cited by 275 · see citing works
Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes
Mabb, A. M., Judson, M. C., Zylka, M. J., & Philpot, B. D. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.04.001 · Cited by 263 · see citing works
EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation
Margolis, S. S., Salogiannis, J., Lipton, D. M., Mandel-Brehm, C., Wills, Z. P., Mardinly, A. R., Hu, L., Greer, P. L., Bikoff, J. B., Ho, H.-Y. H., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.038 · Cited by 256 · see citing works
Ubiquitination in postsynaptic function and plasticity
Mabb, A. M., & Ehlers, M. D. (2010) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100109-104129 · Cited by 255 · see citing works
Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model
Silva-Santos, S., van Woerden, G. M., Bruinsma, C. F., Mientjes, E., Jolfaei, M. A., Distel, B., Kushner, S. A., & Elgersma, Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80554 · Cited by 238 · see citing works
Maternal Loss of Ube3a Produces an Excitatory/Inhibitory Imbalance through Neuron Type-Specific Synaptic Defects
Wallace, M. L., Burette, A. C., Weinberg, R. J., & Philpot, B. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.036 · Cited by 196 · see citing works
Reversing Neurodevelopmental Disorders in Adults
Ehninger, D., Li, W., Fox, K., Stryker, M. P., & Silva, A. J. (2008) · Neuron · doi:10.1016/j.neuron.2008.12.007 · Cited by 196 · see citing works
An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A
Yi, J. J., Berrios, J., Newbern, J. M., Snider, W. D., Philpot, B. D., Hahn, K. M., & Zylka, M. J. (2015) · Cell · doi:10.1016/j.cell.2015.06.045 · Cited by 177 · see citing works
The spectrum of mutations in UBE3A causing Angelman syndrome
Fang, P. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.129 · Cited by 159 · see citing works
Protein degradation, as with protein synthesis, is required during not only long-term spatial memory consolidation but also reconsolidation
Artinian, J., McGauran, A. T., De Jaeger, X., Mouledous, L., Frances, B., & Roullet, P. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06262.x · Cited by 145 · see citing works
Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness
Ingason, A., Kirov, G., Giegling, I., Hansen, T., Isles, A. R., Jakobsen, K. D., Kristinsson, K. T., le Roux, L., Gustafsson, O., Craddock, N., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09111660 · Cited by 114 · see citing works
Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications
Herzing, L. B. K. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.15.1707 · Cited by 109 · see citing works
Degradation of Postsynaptic Scaffold GKAP and Regulation of Dendritic Spine Morphology by the TRIM3 Ubiquitin Ligase in Rat Hippocampal Neurons
Hung, A. Y., Sung, C. C., Brito, I. L., & Sheng, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009842 · Cited by 106 · see citing works
Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome
Su, H., Fan, W., Coskun, P. E., Vesa, J., Gold, J.-A., Jiang, Y.-H., Potluri, P., Procaccio, V., Acab, A., Weiss, J. H., et al. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2009.06.079 · Cited by 80 · see citing works
Self-citation
Ube3a Imprinting Impairs Circadian Robustness in Angelman Syndrome Models
Shi, S.-Q., Bichell, T. J., Ihrie, R. A., & Johnson, C. H. (2015) · Current Biology · doi:10.1016/j.cub.2014.12.047 · Cited by 84 · see citing works
Adult Ube3a Gene Reinstatement Restores the Electrophysiological Deficits of Prefrontal Cortex Layer 5 Neurons in a Mouse Model of Angelman Syndrome
Rotaru, D. C., van Woerden, G. M., Wallaard, I., & Elgersma, Y. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0083-18.2018 · Cited by 74 · see citing works
A critical role for protein degradation in the nucleus accumbens core in cocaine reward memory
Ren, Z.-Y., Liu, M.-M., Xue, Y.-X., Ding, Z.-B., Xue, L.-F., Zhai, S.-D., & Lu, L. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.243 · Cited by 73 · see citing works
Loss of dopaminergic neurons and resulting behavioural deficits in mouse model of Angelman syndrome
Mulherkar, S. A., & Jana, N. R. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.08.002 · Cited by 71 · see citing works
Maternal Loss ofUbe3aImpairs Experience-Driven Dendritic Spine Maintenance in the Developing Visual Cortex
Kim, H., Kunz, P. A., Mooney, R., Philpot, B. D., & Smith, S. L. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4204-15.2016 · Cited by 65 · see citing works
Recent advances in gene therapy for neurodevelopmental disorders with epilepsy
Turner, T. J., Zourray, C., Schorge, S., & Lignani, G. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15168 · Cited by 71 · see citing works
Protein homeostasis and aging: Role of ubiquitin protein ligases
Jana, N. R. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.02.009 · Cited by 67 · see citing works
Enzyme-substrate relationships in the ubiquitin system: approaches for identifying substrates of ubiquitin ligases
O’Connor, H. F., & Huibregtse, J. M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2529-6 · Cited by 42 · see citing works
Stem cells and modeling of autism spectrum disorders
Freitas, B. C. G., Trujillo, C. A., Carromeu, C., Yusupova, M., Herai, R. H., & Muotri, A. R. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2012.09.017 · Cited by 27 · see citing works
Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome
Sidorov, M. S., Judson, M. C., Kim, H., Rougie, M., Ferrer, A. I., Nikolova, V. D., Riddick, N. V., Moy, S. S., & Philpot, B. D. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2828-17.2018 · Cited by 25 · see citing works
What does genetics tell us about imprinting and the placenta connection?
Varmuza, S., & Miri, K. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1714-0 · Cited by 22 · see citing works
Angelman syndrome: advancing the research frontier of neurodevelopmental disorders
Philpot, B. D., Thompson, C. E., Franco, L., & Williams, C. A. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-010-9066-z · Cited by 17 · see citing works
Dynamic shift in localization of UBE3A across developmental stages in an Angelman syndrome mouse model
Gupta, P. K., Feuermann, Y., & Kaphzan, H. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106912 · Cited by 5 · see citing works

Development of an ASO therapy for Angelman syndrome by targeting an evolutionarily conserved region at the start of the UBE3A-AS transcriptPreprint
Dindot, S. V., Christian, S., Murphy, W. J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.27.453820 · Cited by 2 · see citing works
Antisense oligonucleotide therapy rescues disturbed brain rhythms and sleep in juvenile and adult mouse models of Angelman syndromePreprint
Lee, D., Chen, W., Kaku, H. N., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.18.496687 · Cited by 3 · see citing works
Antisense oligonucleotide therapy rescues disturbed brain rhythms and sleep in juvenile and adult mouse models of Angelman syndrome
Lee, D., Chen, W., Kaku, H. N., Zhuo, X., Chao, E. S., Soriano, A., Kuncheria, A., Flores, S., Kim, J. H., Rivera, A. M., et al. (2023) · eLife · doi:10.7554/elife.81892 · Cited by 36 · see citing works
Self-citation
UBE3A reinstatement as a disease‐modifying therapy for Angelman syndrome
Elgersma, Y., & Sonzogni, M. (2021) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14831 · Cited by 55 · see citing works
Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice
Sell, G. L., Xin, W., Cook, E. K., Zbinden, M. A., Schaffer, T., O’Meally, R. N., Cole, R. N., Bonci, A., & Margolis, S. S. (2021) · Scientific Reports · doi:10.1038/s41598-021-97898-w · Cited by 26 · see citing works

Authors: Jiang, Y.-H., Armstrong, D., Albrecht, U., Atkins, C. M., Noebels, J. L., Eichele, G., Sweatt, J. D., & Beaudet, A. L.
Affiliations: Baylor College of Medicine (US)
Howard Hughes Medical Institute (US)
Corresponding author: Beaudet, Arthur L
ORCID: Jiang, Yong-hui
Albrecht, Urs
Atkins, Coleen M
Noebels, Jeffrey L
Sweatt, J.David
Beaudet, Arthur L
Venue: Neuron
Publisher: Elsevier BV
Published: 1998-10
Volume: 21
Issue: 4
Pages: 799-811
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(00)80596-6
OpenAlex: W1983532821
Cited by: 852
References: 72
Citations by year: 2026: 14 · 2025: 32 · 2024: 29 · 2023: 29 · 2022: 38 · 2021: 32 · 2020: 44 · 2019: 31 · 2018: 31 · 2017: 42 · 2016: 31 · 2015: 41 · 2014: 30 · 2013: 39 · 2012: 38
FWCI: 10.27
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5403 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: National Institute of Mental Health (MH 57014, R01MH057014)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: Angelman syndrome, UBE3A, p53, cytoplasmic p53, long-term potentiation, contextual learning, imprinting, motor impairment, seizures, synaptic plasticity, postmitotic neurons, ubiquitination
MeSH terms: Acoustic Stimulation, Animals, Association Learning, Brain, Cytoplasm, Disease Models, Animal, Learning Disabilities, Ligases, Motor Activity, Mutation, Neurons, Seizures, Synapses, Tumor Suppressor Protein p53, Long-Term Potentiation, Ubiquitin-Protein Ligases, Mice

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Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation

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