Functional characterization of the chaperone network connected with the human ribosome-associated complex (mRAC)

与新合成多肽相互作用的哺乳动物伴侣网络不同于酵母和其他低等真核生物。该项目的目标是识别、编目和描述与哺乳动物翻译机制合作的伴侣组。具体来说，我们希望了解哺乳动物核糖体相关复合体（mRAC）的功能，该复合体由Hsp70同源物Hsp70L1和j结构域蛋白MPP11组成。mRAC与它的远亲酵母在几个方面不同。首先，酵母RAC与真菌特异性核糖体结合的Hsp70密切合作，而在哺乳动物细胞质中没有明显的同源物。其次，MPP11包含一个c端延伸，与转录激活子的Myb结构域同源。在体内和体外对mRAC的功能进行详细分析。我们想要确定是否有任何已知的哺乳动物细胞质Hsp70同源物与mRAC合作，并旨在确定在翻译机制中进化起作用的Hsp70。关于MPP11的Myb结构域，我们将跟进初步证据，表明mRAC除了其核糖体作用外还具有其他功能。

Mammalian chaperone networks interacting with newly synthesized polypeptides are distinct from yeast and other lower eukaryotes. Goal of the project is to identify, catalogue, and characterize the sets of chaperones that cooperate with the mammalian translation machinery. Specifically, we want to understand the function of the mammalian ribosome-associated complex (mRAC), consisting of the Hsp70 homolog Hsp70L1 and the J-domain protein MPP11. mRAC differs from its distantly related yeast counterpart in several aspects. First, yeast RAC closely cooperates with a fungi-specific ribosome-bound Hsp70 for which there is no apparent homolog in the mammalian cytosol. Second, MPP11 contains a C-terminal extension homologous to the Myb domain of transcriptional activators. mRAC function shall be analyzed in detail in vivo and in vitro. We want to establish whether any of the known mammalian cytosolic Hsp70 homologs cooperate with mRAC, and aim to identify Hsp70s that evolved to function in the context of the translation machinery. With respect to MPP11´s Myb domain we will follow up on preliminary evidence suggesting that mRAC serves additional functions beyond its ribosomal role.