Nucleolar targets of chemotherapy involved in cell cycle and growth control

in München

Target genes of the onco-protein Myc coordinate cell growth and proliferation. Myc target genes with nucleolar functions play a central role in ribosome biogenesis, a cellular process, which is also required for destabilization of the tumor suppressor protein p53 in proliferating cells. Aim of the project is to unravel the molecular mechanisms and signaling pathways leading to p53 stabilization after inhibition of ribosome biogenesis.

Previously we have identified and characterized the c-myc target genes pes1, bop1, and wdr12. Their products form a trimeric complex, PeBoW, which is essential for processing of ribosomal RNA. Knockdown of PeBoW-components or other ribosome biogenesis factors consistently induce a stabilization of p53 and cell cycle arrest. We could now show that a large number of chemotherapeutic drugs inhibit ribosome biogenesis either at the level of rRNA transcription, or at the levels of early or late rRNA processing. These and other observations led to the current model that functional ribosome biogenesis is a prerequisite for destabilization of p53 in proliferating cells.


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Prof. Dr. Dirk Eick
Department of Molecular Epigenetics Helmholtz-Zentrum-München Marchioninistrasse 25 D-81377 Munich, Germany

Phone: +49-89-7099512
Fax: +49-89-7099500