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

• Applicant: Professorin Dr. Sabine Karola Rospert
• Subject Area: Biochemistry
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 28423497

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.

• DFG Programme: Research Grants