BBVA Foundation-CNIO Cancer Cell Biology Program, Spanish National Cancer Centre (CNIO), c/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Ann Rheum Dis. 2010 Jan;69 Suppl 1:i86-88. doi: 10.1136/ard.2009.119396.
The Fos and Jun proteins are members of the AP-1 transcription factor complex, which is a central regulator for many cellular functions. This paper summarises the important functions of Fos proteins in bone development, with special emphasis on the Fos-related proteins Fra-1 and Fra-2. These factors determine the functions of osteoblasts and osteoclasts and regulate cytokine signalling during bone development. Likewise, the Jun proteins control the expression of cytokines and chemokines and are probably causally involved in inflammatory skin diseases such as psoriasis. Investigations into the molecular mechanisms responsible for skin inflammation have revealed that Jun proteins control cytokine expression, such as granulocyte colony-stimulating factor, IL-6 and tumour necrosis factor alpha by transcriptional and posttranscriptional pathways. Finally, the paper discusses the relevance of the Jun-dependent mouse model for psoriasis for preclinical studies in the field of anti-angiogenic therapies.
Fos 和 Jun 蛋白是 AP-1 转录因子复合物的成员,该复合物是许多细胞功能的中央调节剂。本文总结了 Fos 蛋白在骨骼发育中的重要功能,特别强调了 Fos 相关蛋白 Fra-1 和 Fra-2。这些因子决定了成骨细胞和破骨细胞的功能,并在骨骼发育过程中调节细胞因子信号转导。同样,Jun 蛋白控制细胞因子和趋化因子的表达,并且可能与银屑病等炎症性皮肤病有因果关系。对导致皮肤炎症的分子机制的研究表明,Jun 蛋白通过转录和转录后途径控制细胞因子的表达,如粒细胞集落刺激因子、IL-6 和肿瘤坏死因子-α。最后,本文讨论了 Jun 依赖性银屑病小鼠模型在抗血管生成治疗领域的临床前研究中的相关性。