Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and small Maf proteins.
Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and small Maf proteins.
复制标题
Maf 核癌蛋白的反式激活活性由 Jun、Fos 和小 Maf 蛋白调节。
作者：
K. Kataoka;M. Noda;M. Nishizawa
V-maf癌基因编码一种核bZip蛋白，它能识别与AP-1位点相关的相对较长的回文序列。在本研究中，我们研究了MAF的反式激活与转化活性的关系。该分子三分之二的氨基末端对于其DNA结合活性来说是不必要的，但却赋予了其反式激活的潜力。一组缺失突变体的反式激活活性与其细胞转化能力有很好的相关性。然而，与致癌活性增强相关的点突变在反式激活方面并不比野生型更有效，这表明MAF的其他功能(S)对其转化能力也是重要的。我们还检测了其他bZip蛋白对MAF反式激活活性的影响。三种缺失v-Maf反式激活结构域的小分子Maf家族蛋白(MafK、Maff和MafG)竞争性地抑制Maf的反式激活。Jun或Fos的共表达还通过形成具有不同DNA结合特异性的Maf/Jun或Maf/Fos异源二聚体来影响MAF的反式激活潜能。除了这些因素外，我们注意到与成纤维细胞中典型的AP-1位点相关的序列与NF-E2位点相关的内源性反式激活活性很强。这些结果表明，真核基因的AP-1位点样顺式调控元件受多组具有不同DNA结合和反式激活特性的bZip二聚体的调控。
The v-maf oncogene encodes a nuclear bZip protein which specifically recognizes relatively long palindromic sequences related to an AP-1 site. In this study, we investigated the relationship of transactivation and transformation activity of Maf. The amino-terminal two thirds of the molecule were dispensable for its DNA-binding activity but conferred its transactivation potential. Transactivation activities of a set of deletion mutants correlated well with their cell transforming abilities. However, a point mutant associated with enhanced oncogenic activity was not more effective in transactivation than the wild type, suggesting that some other function(s) of Maf is also important for its transforming ability. We also examined the effect of other bZip proteins on the transactivation activity of Maf. Three small Maf family proteins (MafK, MafF and MafG), which are missing the transactivation domain of v-Maf, competitively inhibited transactivation by Maf. Co-expression of Jun or Fos also affected the transactivation potential of Maf by forming Maf/Jun or Maf/Fos heterodimers of distinct DNA-binding specificities. In addition to these factors, we noticed the presence of a strong endogenous transactivating activity associated with a sequence related to an NF-E2 site rather than the typical AP-1 site in fibroblast cells. These results indicate that AP-1 site-like cis-regulatory elements of eukaryotic genes are regulated by multiple sets of bZip dimers with different DNA-binding and transactivation properties.