泛素蛋白连接酶E3A的表观遗传调控及其在人类神经发育障碍中的作用。
Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders.
作者信息
LaSalle Janine M, Reiter Lawrence T, Chamberlain Stormy J
机构信息
Medical Microbiology & Immunology, Genome Center & MIND Institute, University of California, Davis, CA 95616, USA.
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
出版信息
Epigenomics. 2015 Oct;7(7):1213-28. doi: 10.2217/epi.15.70. Epub 2015 Nov 20.
The E3 ubiquitin ligase UBE3A, also known as E6-AP, has a multitude of ascribed functions and targets relevant to human health and disease. Epigenetic regulation of the UBE3A gene by parentally imprinted noncoding transcription within human chromosome 15q11.2-q13.3 is responsible for the maternal-specific effects of 15q11.2-q13.3 deletion or duplication disorders. Here, we review the evidence for diverse and emerging roles for UBE3A in the proteasome, synapse and nucleus in regulating protein stability and transcription as well as the current mechanistic understanding of UBE3A imprinting in neurons. Angelman and Dup15q syndromes as well as experimental models of these neurodevelopmental disorders are highlighted as improving understanding of UBE3A and its complex regulation for improving therapeutic strategies.
E3泛素连接酶UBE3A，也称为E6-AP，具有许多与人类健康和疾病相关的既定功能和靶点。人类染色体15q11.2-q13.3内亲本印记的非编码转录对UBE3A基因的表观遗传调控，是15q11.2-q13.3缺失或重复障碍产生母系特异性效应的原因。在此，我们综述了UBE3A在蛋白酶体、突触和细胞核中调节蛋白质稳定性和转录的多种新出现作用的证据，以及目前对神经元中UBE3A印记的机制理解。天使综合征和Dup15q综合征以及这些神经发育障碍的实验模型被重点提及，它们有助于加深对UBE3A及其复杂调控的理解，从而改进治疗策略。
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