Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice

Science Translational Medicine

Volumn 3, Issue 103, 2011, Pages

  Smith, Stephen E P ^a   Zhou, Yu Dong ^a   Zhang, Guangping ^a   Jin, Zhe ^a   Stoppel, David C ^a   Anderson, Matthew P ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUTAMIC ACID; UBIQUITIN PROTEIN LIGASE E3; UBE3A PROTEIN, MOUSE; UBIQUITIN PROTEIN LIGASE;

ALLELE; AMINO ACID SYNTHESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTISM; CHROMOSOME 15Q; CHROMOSOME DUPLICATION; COMMUNICATION DISORDER; COMPULSION; CONTROLLED STUDY; COPY NUMBER VARIATION; DICENTRIC CHROMOSOME; DISEASE ASSOCIATION; E3 UBIQUITIN PROTEIN LIGASE GENE; EMBRYO; FEMALE; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENETIC ASSOCIATION; MALE; NERVE CELL STIMULATION; NONHUMAN; PRESYNAPTIC POTENTIAL; PRIORITY JOURNAL; SOCIAL DISABILITY; SOCIAL INTERACTION; STEREOTYPY; SYNAPTIC TRANSMISSION; ANIMAL; ELECTROPHYSIOLOGY; GENETICS; METABOLISM; MOUSE; PHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; AUTISTIC DISORDER; ELECTROPHYSIOLOGY; GLUTAMIC ACID; MICE; MICE, TRANSGENIC; SYNAPTIC TRANSMISSION; UBIQUITIN-PROTEIN LIGASES;

EID: 80053626726     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002627     Document Type: Article

References (61)

1. S. E. Levy, D. S. Mandell, R. T. Schultz, Autism. Lancet 374, 1627-1638 (2009).
2. B. S. Abrahams, D. H. Geschwind, Advances in autism genetics: On the threshold of a new neurobiology. Nat. Rev. Genet. 9, 341-355 (2008).
3. J. T. Glessner, K. Wang, G. Cai, O. Korvatska, C. E. Kim, S. Wood, H. Zhang, A. Estes, C. W. Brune, J. P. Bradfield, M. Imielinski, E. C. Frackelton, J. Reichert, E. L. Crawford, J. Munson, P. M. Sleiman, R. Chiavacci, K. Annaiah, K. Thomas, C. Hou, W. Glaberson, J. Flory, F. Otieno, M. Garris, L. Soorya, L. Klei, J. Piven, K. J. Meyer, E. Anagnostou, T. Sakurai, R. M. Game, D. S. Rudd, D. Zurawiecki, C. J. McDougle, L. K. Davis, J. Miller, D. J. Posey, S. Michaels, A. Kolevzon, J. M. Silverman, R. Bernier, S. E. Levy, R. T. Schultz, G. Dawson, T. Owley, W. M. McMahon, T. H. Wassink, J. A. Sweeney, J. I. Nurnberger, H. Coon, J. S. Sutcliffe, N. J. Minshew, S. F. Grant, M. Bucan, E. H. Cook, J. D. Buxbaum, B. Devlin, G. D. Schellenberg, H. Hakonarson, Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459, 569-573 (2009).
4. E.M. Morrow, S. Y. Yoo, S. W. Flavell, T. K. Kim, Y. Lin, R. S. Hill, N. M. Mukaddes, S. Balkhy, G. Gascon, A. Hashmi, S. Al-Saad, J. Ware, R. M. Joseph, R. Greenblatt, D. Gleason, J. A. Ertelt, K. A. Apse, A. Bodell, J. N. Partlow, B. Barry, H. Yao, K. Markianos, R. J. Ferland, M. E. Greenberg, C. A. Walsh, Identifying autism loci and genes by tracing recent shared ancestry. Science 321, 218-223 (2008).
5. D. Pinto, A. T. Pagnamenta, L. Klei, R. Anney, D. Merico, R. Regan, J. Conroy, T. R. Magalhaes, C. Correia, B. S. Abrahams, J. Almeida, E. Bacchelli, G. D. Bader, A. J. Bailey, G. Baird, A. Battaglia, T. Berney, N. Bolshakova, S. Bölte, P. F. Bolton, T. Bourgeron, S. Brennan, J. Brian, S. E. Bryson, A. R. Carson, G. Casallo, J. Casey, B. H. Chung, L. Cochrane, C. Corsello, E. L. Crawford, A. Crossett, C. Cytrynbaum, G. Dawson, M. De Jonge, R. Delorme, I. Drmic, E. Duketis, F. Duque, A. Estes, P. Farrar, B. A. Fernandez, S. E. Folstein, E. Fombonne, C. M. Freitag, J. Gilbert, C. Gillberg, J. T. Glessner, J. Goldberg, A. Green, J. Green, S. J. Guter, H. Hakonarson, E. A. Heron, M. Hill, R. Holt, J. L. Howe, G. Hughes, V. Hus, R. Igliozzi, C. Kim, S. M. Klauck, A. Kolevzon, O. Korvatska, V. Kustanovich, C. M. Lajonchere, J. A. Lamb, M. Laskawiec, M. Leboyer, A. Le Couteur, B. L. Leventhal, A. C. Lionel, X. Q. Liu, C. Lord, L. Lotspeich, S. C. Lund, E. Maestrini,W.Mahoney, C. Mantoulan, C. R. Marshall, H. McConachie, C. J. McDougle, J. McGrath, W. M. McMahon, A. Merikangas, O. Migita, N. J. Minshew, G. K. Mirza, J. Munson, S. F. Nelson, C. Noakes, A. Noor, G. Nygren, G. Oliveira, K. Papanikolaou, J. R. Parr, B. Parrini, T. Paton, A. Pickles, M. Pilorge, J. Piven, C. P. Ponting, D. J. Posey, A. Poustka, F. Poustka, A. Prasad, J. Ragoussis, K. Renshaw, J. Rickaby, W. Roberts, K. Roeder, B. Roge, M. L. Rutter, L. J. Bierut, J. P. Rice, J. Salt, K. Sansom, D. Sato, R. Segurado, A. F. Sequeira, L. Senman, N. Shah, V. C. Sheffield, L. Soorya, I. Sousa, O. Stein, N. Sykes, V. Stoppioni, C. Strawbridge, R. Tancredi, K. Tansey, B. Thiruvahindrapduram, A. P. Thompson, S. Thomson, A. Tryfon, J. Tsiantis, H. Van Engeland, J. B. Vincent, F. Volkmar, S. Wallace, K. Wang, Z. Wang, T. H. Wassink, C. Webber, R. Weksberg, K. Wing, K. Wittemeyer, S. Wood, J. Wu, B. L. Yaspan, D. Zurawiecki, L. Zwaigenbaum, J. D. Buxbaum, R. M. Cantor, E. H. Cook, H. Coon, M. L. Cuccaro, B. Devlin, S. Ennis, L. Gallagher, D. H. Geschwind, M. Gill, J. L. Haines, J. Hallmayer, J. Miller, A. P. Monaco, J. I. Nurnberger Jr., A. D. Paterson, M. A. Pericak-Vance, G. D. Schellenberg, P. Szatmari, A. M. Vicente, V. J. Vieland, E. M. Wijsman, S.W. Scherer, J. S. Sutcliffe, C. Betancur, Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368-372 (2010).
6. J. Sebat, B. Lakshmi, D. Malhotra, J. Troge, C. Lese-Martin, T. Walsh, B. Yamrom, S. Yoon, A. Krasnitz, J. Kendall, A. Leotta, D. Pai, R. Zhang, Y. H. Lee, J. Hicks, S. J. Spence, A. T. Lee, K. Puura, T. Lehtimäki, D. Ledbetter, P. K. Gregersen, J. Bregman, J. S. Sutcliffe, V. Jobanputra, W. Chung, D. Warburton, M. C. King, D. Skuse, D. H. Geschwind, T. C. Gilliam, K. Ye, M. Wigler, Strong association of de novo copy number mutations with autism. Science 316, 445-449 (2007).
7. L. A. Weiss, Y. Shen, J. M. Korn, D. E. Arking, D. T. Miller, R. Fossdal, E. Saemundsen, H. Stefansson, M. A. Ferreira, T. Green, O. S. Platt, D. M. Ruderfer, C. A. Walsh, D. Altshuler, A. Chakravarti, R. E. Tanzi, K. Stefansson, S. L. Santangelo, J. F. Gusella, P. Sklar, B. L. Wu, M. J. Daly; Autism Consortium, Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667-675 (2008).
8. A. Hogart, D. Wu, J. M. LaSalle, N. C. Schanen, The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13. Neurobiol. Dis. 38, 181-191 (2010).
9. U. Albrecht, J. S. Sutcliffe, B. M. Cattanach, C. V. Beechey, D. Armstrong, G. Eichele, A. L. Beaudet, Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat. Genet. 17, 75-78 (1997).
10. Y. H. Jiang, D. Armstrong, U. Albrecht, C. M. Atkins, J. L. Noebels, G. Eichele, J. D. Sweatt, A. L. Beaudet, Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron 21, 799-811 (1998).
11. T. Kishino, M. Lalande, J. Wagstaff, UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet. 15, 70-73 (1997).
12. S. V. Dindot, B. A. Antalffy, M. B. Bhattacharjee, A. L. Beaudet, The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum. Mol. Genet. 17, 111-118 (2008).
13. Y. H. Jiang, Y. Pan, L. Zhu, L. Landa, J. Yoo, C. Spencer, I. Lorenzo, M. Brilliant, J. Noebels, A. L. Beaudet, Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3. PLoS One 5, e12278 (2010).
14. E. J. Weeber, Y. H. Jiang, Y. Elgersma, A. W. Varga, Y. Carrasquillo, S. E. Brown, J. M. Christian, B. Mirnikjoo, A. Silva, A. L. Beaudet, J. D. Sweatt, Derangements of hippocampal calcium/ calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome. J. Neurosci. 23, 2634-2644 (2003).
15. G.M. Van Woerden, K. D. Harris,M. R. Hojjati, R.M. Gustin, S. Qiu, R. De Avila Freire, Y. H. Jiang, Y. Elgersma, E. J. Weeber, Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of aCaMKII inhibitory phosphorylation. Nat. Neurosci. 10, 280-282 (2007).
16. M. Sato, M. P. Stryker, Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proc. Natl. Acad. Sci. U.S.A. 107, 5611-5616 (2010).
17. K. Yashiro, T. T. Riday, K. H. Condon, A. C. Roberts, D. R. Bernardo, R. Prakash, R. J. Weinberg, M. D. Ehlers, B. D. Philpot, Ube3a is required for experience-dependent maturation of the neocortex. Nat. Neurosci. 12, 777-783 (2009).
18. M. Scheffner, J. M. Huibregtse, R. D. Vierstra, P. M. Howley, The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75, 495-505 (1993).
19. P. L. Greer, R. Hanayama, B. L. Bloodgood, A. R. Mardinly, D. M. Lipton, S. W. Flavell, T. K. Kim, E. C. Griffith, Z. Waldon, R. Maehr, H. L. Ploegh, S. Chowdhury, P. F. Worley, J. Steen, M. E. Greenberg, The Angelman syndrome protein Ube3A regulates synapse development by ubiquitinating Arc. Cell 140, 704-716 (2010).
20. S. S. Margolis, J. Salogiannis, D. M. Lipton, C. Mandel-Brehm, Z. P. Wills, A. R. Mardinly, L. Hu, P. L. Greer, J. B. Bikoff, H. Y. Ho, M. J. Soskis, M. Sahin, M. E. Greenberg, EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell 143, 442-455 (2010).
21. Y. D. Zhou, S. Lee, Z. Jin, M. Wright, S. E. Smith, M. P. Anderson, Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat. Med. 15, 1208-1214 (2009).
22. M. Landers, D. L. Bancescu, E. Le Meur, C. Rougeulle, H. Glatt-Deeley, C. Brannan, F. Muscatelli, M. Lalande, Regulation of the large (~1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn. Nucleic Acids Res. 32, 3480-3492 (2004).
23. R. M. Gustin, T. J. Bichell, M. Bubser, J. Daily, I. Filonova, D. Mrelashvili, A. Y. Deutch, R. J. Colbran, E. J. Weeber, K. F. Haas, Tissue-specific variation of Ube3a protein expression in rodents and in a mouse model of Angelman syndrome. Neurobiol. Dis. 39, 283-291 (2010).
24. J. N. Crawley, Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol. 17, 448-459 (2007).
25. S. E. Smith, J. Li, K. Garbett, K. Mirnics, P. H. Patterson, Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci. 27, 10695-10702 (2007).
26. T. E. Holy, Z. Guo, Ultrasonic songs of male mice. PLoS Biol. 3, e386 (2005).
27. G. Ehret, Infant rodent ultrasounds-A gate to the understanding of sound communication. Behav. Genet. 35, 19-29 (2005).
28. J. Blundell, C. A. Blaiss, M. R. Etherton, F. Espinosa, K. Tabuchi, C. Walz, M. F. Bolliger, T. C. Südhof, C. M. Powell, Neuroligin-1 deletion results in impaired spatialmemory and increased repetitive behavior. J. Neurosci. 30, 2115-2129 (2010).
29. M. R. Etherton, C. A. Blaiss, C. M. Powell, T. C. Sudhof, Mouse neurexin-1a deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc. Natl. Acad. Sci. U.S.A. 106, 17998-18003 (2009).
30. K. Tabuchi, J. Blundell, M. R. Etherton, R. E. Hammer, X. Liu, C. M. Powell, T. C. Sudhof, A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318, 71-76 (2007).
31. H. T. Chao, H. Chen, R. C. Samaco, M. Xue, M. Chahrour, J. Yoo, J. L. Neul, S. Gong, H. C. Lu, N. Heintz, M. Ekker, J. L. Rubenstein, J. L. Noebels, C. Rosenmund, H. Y. Zoghbi, Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468, 263-269 (2010).
32. G. Liu, S. Choi, R. W. Tsien, Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices. Neuron 22, 395-409 (1999).
33. K. K. Chadman, S. Gong, M. L. Scattoni, S. E. Boltuck, S. U. Gandhy, N. Heintz, J. N. Crawley, Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res. 1, 147-158 (2008).
34. M. A. Bangash, J. M. Park, T. Melnikova, D. Wang, S. K. Jeon, D. Lee, S. Syeda, J. Kim, M. Kouser, J. Schwartz, Y. Cui, X. Zhao, H. E. Speed, S. E. Kee, J. C. Tu, J. H. Hu, R. S. Petralia, D. J. Linden, C. M. Powell, A. Savonenko, B. Xiao, P. F. Worley, Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism. Cell 145, 758-772 (2011).
35. X. Wang, P. A. McCoy, R. M. Rodriguiz, Y. Pan, H. S. Je, A. C. Roberts, C. J. Kim, J. Berrios, J. S. Colvin, D. Bousquet-Moore, I. Lorenzo, G. Wu, R. J. Weinberg, M. D. Ehlers, B. D. Philpot, A. L. Beaudet, W. C. Wetsel, Y. H. Jiang, Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet. 20, 3093-3108 (2011).
36. J. Peça, C. Feliciano, J. T. Ting, W. Wang, M. F. Wells, T. N. Venkatraman, C. D. Lascola, Z. Fu, G. Feng, Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472, 437-442 (2011).
37. O. Bozdagi, T. Sakurai, D. Papapetrou, X. Wang, D. L. Dickstein, N. Takahashi, Y. Kajiwara, M. Yang, A. M. Katz, M. L. Scattoni, M. J. Harris, R. Saxena, J. L. Silverman, J. N. Crawley, Q. Zhou, P. R. Hof, J. D. Buxbaum, Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol. Autism 1, 15 (2010).
38. The Dutch-Belgian Fragile X Consorthium; C. E. Bakker, C. Verheij, R. Willemsen, R. van der Helm, F. Oerlemans, M. Vermey, A. Bygrave, A. T. Hoogeveen, B. A. Oostra, E. Reyniers, K. De Boule, R. D'Hooge, P. Cras, D. van Velzen, G. Nagels, J.-J.Martin, P. P. DeDeyn, J. K. Darby, P. J. Willems, Fmr1 knockout mice: A model to study fragile X mental retardation. Cell 78, 23-33 (1994).
39. M. Shahbazian, J. Young, L. Yuva-Paylor, C. Spencer, B. Antalffy, J. Noebels, D. Armstrong, R. Paylor, H. Zoghbi, Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35, 243-254 (2002).
40. H. G. McFarlane, G. K. Kusek, M. Yang, J. L. Phoenix, V. J. Bolivar, J. N. Crawley, Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 7, 152-163 (2008).
41. S. M. Hamilton, C. M. Spencer, W. R. Harrison, L. A. Yuva-Paylor, D. F. Graham, R. A. Daza, R. F. Hevner, P. A. Overbeek, R. Paylor, Multiple autism-like behaviors in a novel transgenic mouse model. Behav. Brain Res. 218, 29-41 (2011).
42. L. Shi, S. H. Fatemi, R. W. Sidwell, P. H. Patterson, Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J. Neurosci. 23, 297-302 (2003).
43. N. R. Dennis, M. W. Veltman, R. Thompson, E. Craig, P. F. Bolton, N. S. Thomas, Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. Am. J. Med. Genet. A 140, 434-441 (2006).
44. C. A. Baron, C. G. Tepper, S. Y. Liu, R. R. Davis, N. J. Wang, N. C. Schanen, J. P. Gregg, Genomic and functional profiling of duplicated chromosome 15 cell lines reveal regulatory alterations in UBE3A-associated ubiquitin-proteasome pathway processes. Hum. Mol. Genet. 15, 853-869 (2006).
45. A. Hogart, K. N. Leung, N. J. Wang, D. J. Wu, J. Driscoll, R. O. Vallero, N. C. Schanen, J. M. LaSalle, Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J. Med. Genet. 46, 86-93 (2009).
46. J. Nakatani, K. Tamada, F. Hatanaka, S. Ise, H. Ohta, K. Inoue, S. Tomonaga, Y. Watanabe, Y. J. Chung, R. Banerjee, K. Iwamoto, T. Kato, M. Okazawa, K. Yamauchi, K. Tanda, K. Takao, T. Miyakawa, A. Bradley, T. Takumi, Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism. Cell 137, 1235-1246 (2009).
47. A. Kashiwagi, M. Meguro, H. Hoshiya, M. Haruta, F. Ishino, T. Shibahara, M. Oshimura, Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulb. J. Hum. Genet. 48, 194-198 (2003).
48. M. Meguro, A. Kashiwagi, K. Mitsuya, M. Nakao, I. Kondo, S. Saitoh, M. Oshimura, A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome. Nat. Genet. 28, 19-20 (2001).
49. T. Kayashima, K. Yamasaki, K. Joh, T. Yamada, T. Ohta, K. Yoshiura, N. Matsumoto, Y. Nakane, T. Mukai, N. Niikawa, T. Kishino, Atp10a, the mouse ortholog of the human imprinted ATP10A gene, escapes genomic imprinting. Genomics 81, 644-647 (2003).
50. Y. Nishimura, C. L. Martin, A. Vazquez-Lopez, S. J. Spence, A. I. Alvarez-Retuerto, M. Sigman, C. Steindler, S. Pellegrini, N. C. Schanen, S. T. Warren, D. H. Geschwind, Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum. Mol. Genet. 16, 1682-1698 (2007).
51. A. Hogart, R. P. Nagarajan, K. A. Patzel, D. H. Yasui, J. M. Lasalle, 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum. Mol. Genet. 16, 691-703 (2007).
52. J. D. Shepherd, G. Rumbaugh, J. Wu, S. Chowdhury, N. Plath, D. Kuhl, R. L. Huganir, P. F. Worley, Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron 52, 475-484 (2006).
53. K. Miura, T. Kishino, E. Li, H. Webber, P. Dikkes, G. L. Holmes, J. Wagstaff, Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice. Neurobiol. Dis. 9, 149-159 (2002).
54. A. Mishra, N. R. Jana, Regulation of turnover of tumor suppressor p53 and cell growth by E6-AP, a ubiquitin protein ligase mutated in Angelman mental retardation syndrome. Cell. Mol. Life Sci. 65, 656-666 (2008).
55. S. A. Mulherkar, J. Sharma, N. R. Jana, The ubiquitin ligase E6-AP promotes degradation of a-synuclein. J. Neurochem. 110, 1955-1964 (2009).
56. F. Ferdousy, W. Bodeen, K. Summers, O. Doherty, O. Wright, N. Elsisi, G. Hilliard, J. M. O'Donnell, L. T. Reiter, Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism. Neurobiol. Dis. 41, 669-677 (2011).
57. L. T. Reiter, T. N. Seagroves, M. Bowers, E. Bier, Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. Hum. Mol. Genet. 15, 2825-2835 (2006).
58. L. Hicke, R. Dunn, Regulation of membrane protein transport by ubiquitin and ubiquitinbinding proteins. Annu. Rev. Cell Dev. Biol. 19, 141-172 (2003).
59. D. Mukhopadhyay, H. Riezman, Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315, 201-205 (2007).
60. Z. Nawaz, D. M. Lonard, C. L. Smith, E. Lev-Lehman, S. Y. Tsai, M. J. Tsai, B. W. O'Malley, The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol. Cell. Biol. 19, 1182-1189 (1999).
61. S. Ramamoorthy, Z. Nawaz, E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors. Nucl. Recept. Signal. 6, e006 (2008).