Molecular analysis of Differentiation-Induced Senescence
Principal investigator: Dr.rer. nat. Uta Kossatz-Böhlert
Through the isolation of mouse liver stem cells from mice with a targetd deletion in the Cullin 3 gene we recently identified a pathway which we called Differentiation-Induced Senescence. This molecular mechanims prevents the generation of hepatic tumor stem cells.
To obtain more inside into the Differentiation-Induced Senescence pathway we want to use an siRNA screen based soft agar assays to identify additional proteins which are able to prevent the generation of tumor stem cells.
We will also analyze Cul3 expression in other human tumors to identify other tissues in which the Differentiation-Induced Senescence pathway is of importance.
List of relevant publications:
U Kossatz, K Breuhahn, B Wolf, M Hardtke-Wolenski, L Wilkens, D Steinemann, S Singer, J D. Singer and NP Malek (2010) The cyclin E regulator cullin 3 prevents mouse hepatic progenitor cells from becoming tumor-initiating cells. J. of Clincal Investigation, 120(11):3820-33.
McEvoy JD, Kossatz U, Malek N, Singer JD (2007) Constitutive turnover of cyclin E by Cul3 maintains quiescence. Mol Cell Biol. 27(10):3651-66