文章：

癌症界的新黑手党

A new MAFia in cancer

原文发布日期：2008-08-14

DOI: 10.1038/nrc2460

类型: Review Article

开放获取: 否

要点：

1. Maf proteins are bZIP transcription factors of the AP1 superfamily, like JUN and FOS.
2. During development, Maf proteins are involved early during tissue specification and later in terminal differentiation.
3. Large Maf proteins, MAFA, MAFB and MAF, are bona fide oncogenes, as demonstrated in tissue culture and animal models and in human cancer.
4. In humans, the large Maf are overexpressed in 50% of multiple myelomas and 60% of angioimmunoblastic T-cell lymphomas. In particular, MAF, MAFB and MAFA genes are translocated to the immunoglobulin heavy chain locus in 8–10% of multiple myelomas.
5. The transforming activity of large Maf proteins is context-dependent and they can occasionally display tumour suppressor-like activity in specific cellular settings.
6. Their transforming activity relies on overexpression, and is regulated by post-translational modifications, notably phosphorylation.
7. In several biological settings, large Maf induce deregulation of cell cycle, cell migration and cell–cell interactions through induction of expression of cyclin D2, ARK5 and integrin β7, respectively.
8. The oncogenic activity of Maf may result, in part, from the acquisition of novel functions.
9. A striking characteristic of Maf proteins in oncogenesis is their ability to enhance the interaction between tumour cells and stromal cells.

要点翻译：

1. Maf蛋白是AP1超家族的bZIP转录因子，与JUN和FOS蛋白类似。
2. 在发育过程中，Maf蛋白早期参与组织特异性分化，后期参与终末分化。
3. 大型Maf蛋白（MAFA、MAFB和MAF）经组织培养、动物模型及人类癌症研究证实为真正的癌基因。
4. 在人类中，约50%的多发性骨髓瘤和60%的血管免疫母细胞性T细胞淋巴瘤存在大型Maf蛋白过表达，其中8%-10%的多发性骨髓瘤病例出现MAF、MAFB和MAFA基因易位至免疫球蛋白重链基因座的现象。
5. 大型Maf蛋白的转化活性具有环境依赖性，在特定细胞环境中偶尔会表现出类似肿瘤抑制因子的活性。
6. 其转化活性依赖于过表达，并受翻译后修饰（尤其是磷酸化）的调控。
7. 在多种生物学环境中，大型Maf蛋白分别通过诱导细胞周期蛋白D2、ARK5和整合素β7的表达，引发细胞周期失调、细胞迁移异常和细胞间相互作用紊乱。
8. Maf蛋白的致癌活性可能部分源于其新功能的获得。
9. 其在肿瘤发生中的一个显著特征是能够增强肿瘤细胞与基质细胞之间的相互作用。

英文摘要：

Like JUN and FOS, the Maf transcription factors belong to the AP1 family. Besides their established role in human cancer — overexpression of the large Maf genes promotes the development of multiple myeloma — they can display tumour suppressor-like activity in specific cellular contexts, which is compatible with their physiological role in terminal differentiation. However, their oncogenic activity relies mostly on the acquisition of new biological functions relevant to cell transformation, the most striking characteristic of Maf oncoproteins being their ability to enhance pathological interactions between tumour cells and the stroma.

摘要翻译： 

与JUN和FOS一样，Maf转录因子也属于AP1家族。除了其在人类癌症中的既定作用——大Maf基因的过度表达促进多发性骨髓瘤的发展——它们在某些细胞环境中还可表现出类似肿瘤抑制因子的活性，这与其在终末分化中的生理作用是一致的。然而，它们的致癌活性主要依赖于获得与细胞转化相关的新生物学功能，Maf癌蛋白最显著的特征是其能够增强肿瘤细胞与基质之间的病理性相互作用。

原文链接：

A new MAFia in cancer