C/EBP family transcription factors are degraded by the proteasome but stabilized by forming dimer
C/EBP family transcription factors are degraded by the proteasome but stabilized by forming dimer
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DOI：
10.1038/sj.onc.1206204
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发表时间：
2003-03-06
期刊：
影响因子：
8
通讯作者：
Onozaki, K
中科院分区：
文献类型：
--
作者：
Hattori, T;Ohoka, N;Onozaki, K
CCAAT/增强子结合蛋白(C/EBP)家族转录因子对组织发育、细胞功能、增殖和分化等多种基因的转录起关键作用。在这里，我们发现抑制性/调节性C/EBP家族蛋白Ig/EBP(C/EBPGamma)和CHOP(C/EBPxi)，但不具有正功能的NF-IL6(C/EBPbeta)，是结构性的多泛素化，随后被蛋白酶体降解。此外，这些蛋白质的泛素化和降解通过它们的亮氨酸拉链结构域形成二聚体而被抑制。NF-IL6中亮氨酸拉链结构域的缺失导致其同源二聚活性的丧失和泛素-蛋白酶体系统对蛋白质的降解。此外，Ig/EBP的亮氨酸拉链结构域取代了NF-IL6的结构域，形成了均二聚体，并得到稳定。这些观察结果表明，哺乳动物细胞装备了一种新的调控系统，消除了失去二聚体伙伴的过量C/EBP家族转录因子。
CCAAT/enhancer-binding protein (C/EBP) family transcription factors are critical for transcription of several genes involved in tissue development and cellular function, proliferation, and differentiation. Here we show that inhibitory/regulatory C/EBP family proteins, Ig/EBP (C/EBPgamma) and CHOP (C/EBPxi), but not positively functioning NF-IL6 (C/EBPbeta), are constitutively multiubiquitinated and subsequently degraded by the proteasome. In addition, ubiquitination and degradation of these proteins are suppressed by forming dimer through their leucine zipper domains. Deletion of leucine zipper domain in NF-IL6 caused the loss of its homodimerization activity and the degradation of protein by the ubiquitin-proteasome system. In addition, Ig/EBP with its leucine zipper domain substituted for that of NF-IL6 formed homodimer and was stabilized. These observations suggest that mammalian cells equip a novel regulatory system abrogating the excess C/EBP family transcription factors bereft of dimerizing partner.