Solnoki Kellie Whitecavage, Sing Allison H, Sofa Caitlyn J, Miller Russell, Ogorzalek Paulina A, Penek Hillary V, Palenchar Jennifer B
Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
Mol Biochem Parasitol. 2012 Feb;181(2):94-101. doi: 10.1016/j.molbiopara.2011.10.004. Epub 2011 Oct 15.
Trypanosoma brucei, the causative agent of African Sleeping Sickness, is replete with unique biochemistry, including unusual features of gene transcription. The parasite also contains over 4500 non-annotated genes, representing novel biochemistry yet to be explored. Using tandem affinity purification (TAP)-tagged TbTFIIB, we identified and subsequently confirmed, one of the non-annotated T. brucei proteins, Tb11.02.4300, as a TbTFIIB-interacting protein. The 49 kDa protein is nuclear and essential for parasite variability as determined by RNA interference studies; hence, the nomenclature T. brucei Essential Nuclear Factor (TbENF). TbENF is shown to interact with DNA in a sequence-independent fashion under the conditions examined. Furthermore, TbENF bears motifs associated with many eukaryotic transcription factors, such as a glutamine-rich region and a leucine zipper, yet TbENF is specific to trypanosomatids making it a potentially attractive therapeutic target. Taken together, our results suggest a role for TbENF in trypanosome gene transcription.
布氏锥虫是非洲昏睡病的病原体,具有独特的生物化学特性,包括基因转录的异常特征。该寄生虫还含有超过4500个未注释基因,代表着尚未探索的新型生物化学特性。我们利用串联亲和纯化(TAP)标记的TbTFIIB,鉴定并随后证实了一种未注释的布氏锥虫蛋白Tb11.02.4300是与TbTFIIB相互作用的蛋白。通过RNA干扰研究确定,这种49 kDa的蛋白位于细胞核内,对寄生虫的变异性至关重要;因此,将其命名为布氏锥虫必需核因子(TbENF)。在所检测的条件下,TbENF以不依赖序列的方式与DNA相互作用。此外,TbENF带有许多真核转录因子相关的基序,如富含谷氨酰胺的区域和亮氨酸拉链,但TbENF是锥虫特有的,这使其成为一个潜在的有吸引力的治疗靶点。综上所述,我们的结果表明TbENF在锥虫基因转录中发挥作用。