Conditional expression of the ubiquitous transcription factor MafK induces erythroleukemia cell differentiation.

Transcription factor NF-E2 activity is thought to be crucial for the transcriptional regulation of many erythroid-specific genes. The three small Maf family proteins (MafF, MafG, and MafK) that are closely related to the c-Maf protooncoprotein constitute half of the NF-E2 activity by forming heterodimers with the large tissue-restricted subunit of NF-E2 called p45. We have established and characterized murine erythroleukemia cells that conditionally overexpress MafK from a metallothionein promoter. The conditional expression of MafK caused accumulation of hemoglobin, an indication of terminal differentiation along the erythroid pathway. Concomitantly, DNA binding activities containing MafK were induced within the MafK-overexpressing cells. These results demonstrate that MafK can promote the erythroid differentiation program in erythroleukemia cells and suggest that the small Maf family proteins are key regulatory molecules for erythroid differentiation. IMAGES:

转录因子NF-E2（Transcription factor NF-E2）的活性被认为对诸多红细胞系特异性基因的转录调控至关重要。与c-Maf原癌蛋白密切相关的三个小Maf家族蛋白（MafF、MafG和MafK），通过与NF-E2的组织限制性大亚基p45形成异二聚体，贡献了NF-E2活性的一半。我们已构建并鉴定了可通过金属硫蛋白启动子条件性过表达MafK的小鼠红白血病细胞系。MafK的条件性表达会引发血红蛋白积累，这是红细胞系终末分化的标志性事件。与此同时，在过表达MafK的细胞内，含有MafK的DNA结合活性被诱导激活。上述结果证实，MafK可促进红白血病细胞的红细胞分化程序，并提示小Maf家族蛋白是红细胞系分化的关键调控分子。图片：