Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University , 930 Nishimitani, Kinokawa, Wakayama 649-6493 , Japan ; Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 , Japan.
Biol Open. 2013 Feb 15;2(2):170-82. doi: 10.1242/bio.20123020. Epub 2012 Nov 23.
During the maternal-to-zygotic transition (MZT), maternal proteins in oocytes are degraded by the ubiquitin-proteasome system (UPS), and new proteins are synthesized from the zygotic genome. However, the specific mechanisms underlying the UPS at the MZT are not well understood. We identified a molecule named zygote-specific proteasome assembly chaperone (ZPAC) that is specifically expressed in mouse gonads, and expression of ZPAC was transiently increased at the mouse MZT. ZPAC formed a complex with Ump1 and associated with precursor forms of 20S proteasomes. Transcription of ZPAC genes was also under the control of an autoregulatory feedback mechanism for the compensation of reduced proteasome activity similar to Ump1 and 20S proteasome subunit gene expression. Knockdown of ZPAC in early embryos caused a significant reduction of proteasome activity and decrease in Ump1 and mature proteasomes, leading to accumulation of proteins that need to be degraded at the MZT and early developmental arrest. Therefore, a unique proteasome assembly pathway mediated by ZPAC is important for progression of the mouse MZT.
在母源到合子过渡（MZT）期间，卵母细胞中的母体蛋白被泛素-蛋白酶体系统（UPS）降解，新的蛋白从合子基因组中合成。然而，MZT 时 UPS 的具体机制尚不清楚。我们鉴定了一种名为合子特异性蛋白酶体组装伴侣（ZPAC）的分子，它在小鼠性腺中特异性表达，并且在小鼠 MZT 时 ZPAC 的表达短暂增加。ZPAC 与 Ump1 形成复合物，并与 20S 蛋白酶体的前体形式相关联。ZPAC 基因的转录也受到自身调节反馈机制的控制，该机制类似于 Ump1 和 20S 蛋白酶体亚基基因表达，用于补偿蛋白酶体活性的降低。在早期胚胎中敲低 ZPAC 会导致蛋白酶体活性显著降低，Ump1 和成熟蛋白酶体减少，导致需要在 MZT 和早期发育停滞时降解的蛋白质积累。因此，由 ZPAC 介导的独特蛋白酶体组装途径对于小鼠 MZT 的进展很重要。
