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Review

The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders

1
Department of Pharmacology, Northwestern University, Chicago, IL 60611, USA
2
Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA
3
Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60201, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2108; https://doi.org/10.3390/cancers12082108
Received: 30 June 2020 / Revised: 24 July 2020 / Accepted: 27 July 2020 / Published: 29 July 2020
(This article belongs to the Special Issue Targeting the Ubiquitin Pathway in Cancer)
The HECT (Homologous to the E6-AP Carboxyl Terminus)-family protein E6AP (E6-associated protein), encoded by the UBE3A 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 UBE3A gene cause Angelman syndrome, a severe neurodevelopmental disorder with autosomal dominant inheritance modified by genomic imprinting on chromosome 15q. Moreover, excess dosage of the UBE3A 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. View Full-Text
Keywords: ubiquitin; viral oncogenesis; oncoproteins; tumor suppressors; Angelman syndrome; autism; small molecules; imprinting; E3 ligase; chromosome 15q ubiquitin; viral oncogenesis; oncoproteins; tumor suppressors; Angelman syndrome; autism; small molecules; imprinting; E3 ligase; chromosome 15q
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MDPI and ACS Style

Owais, A.; Mishra, R.K.; Kiyokawa, H. The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders. Cancers 2020, 12, 2108. https://doi.org/10.3390/cancers12082108

AMA Style

Owais A, Mishra RK, Kiyokawa H. The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders. Cancers. 2020; 12(8):2108. https://doi.org/10.3390/cancers12082108

Chicago/Turabian Style

Owais, Asia, Rama K. Mishra, and Hiroaki Kiyokawa. 2020. "The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders" Cancers 12, no. 8: 2108. https://doi.org/10.3390/cancers12082108

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