The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions
UBE3A is a gene implicated in neurodevelopmental disorders. The protein product of UBE3A is the E3 ligase E6-associated protein (E6AP), and its expression in the brain is uniquely regulated via genetic imprinting. Loss of E6AP expression leads to the development of Angelman syndrome (AS), clinically...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-04-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00109/full |
| _version_ | 1819140411292123136 |
|---|---|
| author | Natasha Khatri Natasha Khatri Heng-Ye Man Heng-Ye Man |
| author_facet | Natasha Khatri Natasha Khatri Heng-Ye Man Heng-Ye Man |
| author_sort | Natasha Khatri |
| collection | DOAJ |
| description | UBE3A is a gene implicated in neurodevelopmental disorders. The protein product of UBE3A is the E3 ligase E6-associated protein (E6AP), and its expression in the brain is uniquely regulated via genetic imprinting. Loss of E6AP expression leads to the development of Angelman syndrome (AS), clinically characterized by lack of speech, abnormal motor development, and the presence of seizures. Conversely, copy number variations (CNVs) that result in the overexpression of E6AP are strongly associated with the development of autism spectrum disorders (ASDs), defined by decreased communication, impaired social interest, and increased repetitive behavior. In this review article, we focus on the neurobiological function of Ube3A/E6AP. As an E3 ligase, many functional target proteins of E6AP have been discovered, including p53, Arc, Ephexin5, and SK2. On a neuronal level, E6AP is widely expressed within the cell, including dendritic arbors, spines, and the nucleus. E6AP regulates neuronal morphological maturation and plays an important role in synaptic plasticity and cortical development. These molecular findings provide insight into our understanding of the molecular events underlying AS and ASDs. |
| first_indexed | 2024-12-22T11:38:08Z |
| format | Article |
| id | doaj.art-656afb995f2749eab39b1f7c9f114c68 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T11:38:08Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-656afb995f2749eab39b1f7c9f114c682022-12-21T18:27:22ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-04-011210.3389/fnmol.2019.00109448792The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological FunctionsNatasha Khatri0Natasha Khatri1Heng-Ye Man2Heng-Ye Man3Department of Biology, Boston University, Boston, MA, United StatesDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United StatesDepartment of Biology, Boston University, Boston, MA, United StatesDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United StatesUBE3A is a gene implicated in neurodevelopmental disorders. The protein product of UBE3A is the E3 ligase E6-associated protein (E6AP), and its expression in the brain is uniquely regulated via genetic imprinting. Loss of E6AP expression leads to the development of Angelman syndrome (AS), clinically characterized by lack of speech, abnormal motor development, and the presence of seizures. Conversely, copy number variations (CNVs) that result in the overexpression of E6AP are strongly associated with the development of autism spectrum disorders (ASDs), defined by decreased communication, impaired social interest, and increased repetitive behavior. In this review article, we focus on the neurobiological function of Ube3A/E6AP. As an E3 ligase, many functional target proteins of E6AP have been discovered, including p53, Arc, Ephexin5, and SK2. On a neuronal level, E6AP is widely expressed within the cell, including dendritic arbors, spines, and the nucleus. E6AP regulates neuronal morphological maturation and plays an important role in synaptic plasticity and cortical development. These molecular findings provide insight into our understanding of the molecular events underlying AS and ASDs.https://www.frontiersin.org/article/10.3389/fnmol.2019.00109/fullneurodevelopementUBE3A (E6AP)autism (ASD)Angelman syndrome (AS)ubiquitinationdendritic pruning |
| spellingShingle | Natasha Khatri Natasha Khatri Heng-Ye Man Heng-Ye Man The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions Frontiers in Molecular Neuroscience neurodevelopement UBE3A (E6AP) autism (ASD) Angelman syndrome (AS) ubiquitination dendritic pruning |
| title | The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions |
| title_full | The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions |
| title_fullStr | The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions |
| title_full_unstemmed | The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions |
| title_short | The Autism and Angelman Syndrome Protein Ube3A/E6AP: The Gene, E3 Ligase Ubiquitination Targets and Neurobiological Functions |
| title_sort | autism and angelman syndrome protein ube3a e6ap the gene e3 ligase ubiquitination targets and neurobiological functions |
| topic | neurodevelopement UBE3A (E6AP) autism (ASD) Angelman syndrome (AS) ubiquitination dendritic pruning |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00109/full |
| work_keys_str_mv | AT natashakhatri theautismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT natashakhatri theautismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT hengyeman theautismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT hengyeman theautismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT natashakhatri autismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT natashakhatri autismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT hengyeman autismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions AT hengyeman autismandangelmansyndromeproteinube3ae6apthegenee3ligaseubiquitinationtargetsandneurobiologicalfunctions |