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Degradation of p63 by Itch.

机译：Itch降解p63。

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Protein degradation, the negative aspect of the protein stability equation, occurs through lysosomal and proteasomal pathways. Proteasomal degradation requires the prior ubiquitylation of the protein through the sequential action of El, E2 and E3 ligases, before transfer to the 26S proteasome and degradation into individual amino acids. There are several hundred E3 ligases, divided into RING, U-box and Hect (Homologous to the E6-associated protein C Terminus) domain families. Two very recent reports, in this issue of Cell Cycle by Rossi et al.,and in PNAS by a different Rossi et al.,have now identified the E3 ligase responsible for the proteosomal degradation of p63,a member of the p53 family (Fig. 1). This is Itch, a Hect and WW-domain ligase, originally identified as the mutant gene at the agouti locus in Itchy mice, whose phenotype includes constant itching and chronic lethal lymphoproliferative disease. Since p63 null mice do not develop skin, die at birth due to dehydration and may have more generalized epithelial abnormalities,4"5 and several genetic human syndromes affecting epidermis and-fimb formation are caused by mutations in TP63 (reviewed in ref. 6, Fig. 2) it is evident that understanding the regulation of TP63 steady state protein level by Itch is of high physiological and pathological relevance.
机译：蛋白质降解是蛋白质稳定性方程的负面方面，是通过溶酶体和蛋白酶体途径发生的。蛋白酶体降解需要先通过E1，E2和E3连接酶的顺序作用使蛋白质先泛素化，然后再转移至26S蛋白酶体并降解为单个氨基酸。有数百种E3连接酶，分为RING，U-box和Hect（与E6相关的蛋白C末端同源）域家族。两篇非常近期的报告，在Rossi等人的本期《细胞周期》中以及另一位Rossi等人的在PNAS中，现已鉴定了负责p53家族p63蛋白水解的E3连接酶（图1）。这是Itch，一种Hect和WW域连接酶，最初被鉴定为Itchy小鼠刺骨基因座处的突变基因，其表型包括持续瘙痒和慢性致死性淋巴细胞增生性疾病。由于p63无效的小鼠不发育皮肤，死于脱水而死，可能具有更普遍的上皮异常[4,5]，以及几种影响表皮和纤维形成的遗传人类综合症是由TP63突变引起的（参见参考文献6，图2）显然，了解Itch对TP63稳态蛋白水平的调节具有很高的生理和病理学意义。

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