Characterization of mammalian pre-ribosomal complexes and their deregulation in cancer.

While it is evident that ribosomal biogenesis is accelerated in cancer cells marked with a distinctive enlargement of nucleoli, the assembly of ribosomes and its deregulation in cancer remains poorly characterized. In our preliminary studies, we developed the method of isolation of native pre-ribosomal complexes from mammalian cells. In the present grant application, we will continue the characterization of a nutrient-dependent assembly of pre-ribosomes (Aim 1) and the roles of ribosomal biogenesis factors in assembly of pre-ribosomes (Aim 2) in primary and cancer cells. Deregulation of assembly of pre-ribosomes in a process of oncogenic transformation will be addressed in the Aim 3 of this study. This study will provide basic mechanisms controlling assembly of pre-ribosomes and identify critical steps involved in accelerating building of ribosomes in cancer. The study will have a valuable impact by providing novel targets to suppress ribosomal biogenesis in cancer.