The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders
The HECT (Homologous to the E6-AP Carboxyl Terminus)-family protein E6AP (E6-associated protein), encoded by the <i>UBE3A</i> gene, is a multifaceted ubiquitin ligase that controls diverse signaling pathways involved in cancer and neurological disorders. The oncogenic role of E6AP in pap...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2108 |
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| author | Asia Owais Rama K. Mishra Hiroaki Kiyokawa |
| author_facet | Asia Owais Rama K. Mishra Hiroaki Kiyokawa |
| author_sort | Asia Owais |
| collection | DOAJ |
| description | The HECT (Homologous to the E6-AP Carboxyl Terminus)-family protein E6AP (E6-associated protein), encoded by the <i>UBE3A</i> gene, is a multifaceted ubiquitin ligase that controls diverse signaling pathways involved in cancer and neurological disorders. The oncogenic role of E6AP in papillomavirus-induced cancers is well known, with its action to trigger p53 degradation in complex with the E6 viral oncoprotein. However, the roles of E6AP in non-viral cancers remain poorly defined. It is well established that loss-of-function alterations of the <i>UBE3A</i> gene cause Angelman syndrome, a severe neurodevelopmental disorder with autosomal dominant inheritance modified by genomic imprinting on chromosome 15q. Moreover, excess dosage of the <i>UBE3A</i> gene markedly increases the penetrance of autism spectrum disorders, suggesting that the expression level of UBE3A must be regulated tightly within a physiologically tolerated range during brain development. In this review, current the knowledge about the substrates of E6AP-mediated ubiquitination and their functions in cancer and neurological disorders is discussed, alongside with the ongoing efforts to pharmacologically modulate this ubiquitin ligase as a promising therapeutic target. |
| first_indexed | 2024-03-10T18:08:28Z |
| format | Article |
| id | doaj.art-bd1e9ea8f5a24f149d1f8ff043a344b4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:08:28Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bd1e9ea8f5a24f149d1f8ff043a344b42023-11-20T08:20:45ZengMDPI AGCancers2072-66942020-07-01128210810.3390/cancers12082108The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological DisordersAsia Owais0Rama K. Mishra1Hiroaki Kiyokawa2Department of Pharmacology, Northwestern University, Chicago, IL 60611, USADepartment of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USADepartment of Pharmacology, Northwestern University, Chicago, IL 60611, USAThe HECT (Homologous to the E6-AP Carboxyl Terminus)-family protein E6AP (E6-associated protein), encoded by the <i>UBE3A</i> gene, is a multifaceted ubiquitin ligase that controls diverse signaling pathways involved in cancer and neurological disorders. The oncogenic role of E6AP in papillomavirus-induced cancers is well known, with its action to trigger p53 degradation in complex with the E6 viral oncoprotein. However, the roles of E6AP in non-viral cancers remain poorly defined. It is well established that loss-of-function alterations of the <i>UBE3A</i> gene cause Angelman syndrome, a severe neurodevelopmental disorder with autosomal dominant inheritance modified by genomic imprinting on chromosome 15q. Moreover, excess dosage of the <i>UBE3A</i> gene markedly increases the penetrance of autism spectrum disorders, suggesting that the expression level of UBE3A must be regulated tightly within a physiologically tolerated range during brain development. In this review, current the knowledge about the substrates of E6AP-mediated ubiquitination and their functions in cancer and neurological disorders is discussed, alongside with the ongoing efforts to pharmacologically modulate this ubiquitin ligase as a promising therapeutic target.https://www.mdpi.com/2072-6694/12/8/2108ubiquitinviral oncogenesisoncoproteinstumor suppressorsAngelman syndromeautism |
| spellingShingle | Asia Owais Rama K. Mishra Hiroaki Kiyokawa The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders Cancers ubiquitin viral oncogenesis oncoproteins tumor suppressors Angelman syndrome autism |
| title | The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders |
| title_full | The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders |
| title_fullStr | The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders |
| title_full_unstemmed | The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders |
| title_short | The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders |
| title_sort | hect e3 ligase e6ap ube3a as a therapeutic target in cancer and neurological disorders |
| topic | ubiquitin viral oncogenesis oncoproteins tumor suppressors Angelman syndrome autism |
| url | https://www.mdpi.com/2072-6694/12/8/2108 |
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