Gpn3在赖氨酸216处发生多聚泛素化，并以一种可被Gpn1抑制的方式在细胞核中被蛋白酶体降解。
Gpn3 is polyubiquitinated on lysine 216 and degraded by the proteasome in the cell nucleus in a Gpn1-inhibitable manner.
作者信息
Méndez-Hernández Lucía E, Robledo-Rivera Angelica Y, Macías-Silva Marina, Calera Mónica R, Sánchez-Olea Roberto
机构信息
Instituto de Física, Universidad Autónoma de San Luis Potosí, México.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México.
出版信息
FEBS Lett. 2017 Nov;591(22):3757-3770. doi: 10.1002/1873-3468.12883. Epub 2017 Oct 27.
Gpn1 associates with Gpn3, and both are required for RNA polymerase II nuclear targeting. Global studies have identified by mass spectrometry that human Gpn3 is ubiquitinated on lysines 189 and 216. Our goals here were to determine the type, physiological importance, and regulation of Gpn3 ubiquitination. After inhibiting the proteasome with MG132, Gpn3-Flag was polyubiquitinated on K216, but not K189, in HEK293T cells. Gpn3-Flag exhibited nucleo-cytoplasmic shuttling, but polyubiquitination and proteasomal degradation of Gpn3-Flag occurred only in the cell nucleus. Polyubiquitination-deficient Gpn3-Flag K216R displayed a longer half-life than Gpn3-Flag in two cell lines. Interestingly, Gpn1-EYFP inhibited Gpn3-Flag polyubiquitination in a dose-dependent manner. In conclusion, Gpn1-inhibitable, nuclear polyubiquitination on lysine 216 regulates the half-life of Gpn3 by tagging it for proteasomal degradation.
Gpn1与Gpn3相互关联，二者对于RNA聚合酶II的核靶向都是必需的。全球范围内的研究通过质谱分析鉴定出人类Gpn3在赖氨酸189和216处发生泛素化。我们在此的目标是确定Gpn3泛素化的类型、生理重要性以及调控机制。在用MG132抑制蛋白酶体后，在HEK293T细胞中，Gpn3-Flag在K216处发生多聚泛素化，但在K189处未发生。Gpn3-Flag表现出核质穿梭现象，但Gpn3-Flag的多聚泛素化和蛋白酶体降解仅发生在细胞核中。在两种细胞系中，多聚泛素化缺陷型的Gpn3-Flag K216R的半衰期比Gpn3-Flag更长。有趣的是，Gpn1-EYFP以剂量依赖性方式抑制Gpn3-Flag的多聚泛素化。总之，赖氨酸216处可被Gpn1抑制的核多聚泛素化通过将Gpn3标记用于蛋白酶体降解来调节其半衰期。
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