Lurie Cancer Center - Basic Sciences Division, Program Information

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Subcellular localization of proteins and DNA

Research Team: Folsch, Hicke, Brickner, Yaseen

Membrane trafficking (Folsch, Hicke)
After synthesis, proteins are sorted to different cellular locations and the localization controls protein function. Folsch is investigating how proteins are sorted between the basolateral and apical membranes in epithelial cells. This process is responsible for the organization of these cells and loss of cell polarity is a key event in the transformation of epithelial cells. Hicke is investigating how proteins are removed from the cell surface by endocytosis. Her laboratory is focusing specifically on how ubiquitin modification of receptors and adapter proteins contributes to the molecular mechanism of membrane flow. This process plays a critical role in regulation of signaling processes, including those that control cell growth and differentiation and therefore affect oncogenesis. As an example, the proto-oncogene Cbl is a protein ubiquitin ligase involved regulation of tyrosine kinase signaling.

Protein and DNA localization (Brickner, Yaseen)

Soluble proteins are also transported to different subcellular compartment. Yaseen investigates how proteins are translocated to the nucleus where many, including those studied by Yaseen, are directly responsible for the regulation of gene expression. It is well accepted that the function of proteins is controlled by their subcellular localization. It is much less well understood how the spatial organization of DNA affects its function. Brickner is investigating how the localization of genes within the nucleus affects their expression focusing on the recruitment of genes to the nuclear membrane during their activation. Transcriptional regulation is fundamentally involved in differentiation and oncogenesis. A cellular understanding of this process will likely illuminate how normal regulation is disrupted during oncogenesis and how this process is coupled to the phenomenon of genomic instability.

Robert H. Lurie Comprehensive Cancer Center of Northwestern University