MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4.

MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4.
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MGRN1依赖性色素类型开关需要其泛素化活性,而不是与TSG101或NEDD4的相互作用。

DOI:
10.1111/pcmr.12059
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发表时间:
2013-03
影响因子:
4.3
通讯作者:
Walker KK
Walker KK
中科院分区:
医学3区
文献类型:
--
作者:
Gunn TM;Silvius D;Bagher P;Sun K;Walker KK

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缺乏E3泛素连接酶mahogunin无名指-1(MGRN 1)的小鼠具有多效性表型,包括海绵状神经变性、胚胎图案缺陷和由于色素类型转换缺陷而导致的深色皮毛。迄今为止,唯一确定的MGRN 1泛素化靶点是肿瘤易感基因101(TSG 101),它是内体运输机制的一个组成部分。在这里,我们表明,MGRN 1也相互作用,但不泛素化NEDD 4,HECT结构域泛素连接酶参与内体运输。使用转基因小鼠,我们证明,色素类型转换可能需要MGRN 1的泛素连接酶活性,但不是它的能力,结合TSG 101或NEDD 4。这表明,MGRN 1依赖泛素化的一个尚未确定的目标蛋白是所需的刺豚鼠介导的黑皮质素信号。
Mice lacking the E3 ubiquitin ligase mahogunin ring finger-1 (MGRN1) have a pleiotropic phenotype that includes spongiform neurodegeneration, embryonic patterning defects, and dark fur due to a defect in pigment-type switching. The only MGRN1 ubiquitination target identified to date is tumor susceptibility gene 101 (TSG101), a component of the endosomal trafficking machinery. Here, we show that MGRN1 also interacts with but does not ubiquitinate NEDD4, a HECT-domain ubiquitin ligase involved in endosomal trafficking. Using transgenesis in mice, we demonstrate that pigment-type switching likely requires MGRN1’s ubiquitin ligase activity but not its ability to bind TSG101 or NEDD4. This indicates that MGRN1-dependent ubiquitination of an as-yet unidentified target protein is required for agouti-mediated melanocortin signaling.
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