Partners in crime: STAT3 and CDK6 control transformation in hematopoietic cells

Oncogenes teaming up – activated STAT3 and STAT5 shaping chromatin in connection with CDK6

NETWORK CONTRIBUTION

We propose a novel mode by which STAT3 regulates the chromatin landscape in transformed haematopoietic cells in cooperation with the cell cycle regulator CDK6. We shall test this notion by means of BCR ABL+ and NPM-ALK+ tumors.. If either STAT3 or CDK6 is absent, tumor formation is severely reduced. Our preliminary studies suggest a tight interaction of STAT3 and CDK6 on chromatin, which we intend to investigate further. Our investigations will include the STAT3 mutations that have been repeatedly found in human lymphoid malignancies. These clinically relevant STAT3 mutations will be studied in model cell lines and in vitro and in vivo in B and T lymphoid cells.

Our major goal is to test the ability of lymphocytes to propagate leukaemia, their epigenetic landscape and their interaction with CDK6. The work should reveal a novel layer of regulation of STAT3, mediated via its interaction with CDK6 and might open a novel therapeutic avenue to interfere with STAT3´s function.

Within the proposed project we aim to determine the stepwise cooperativity of STAT3 and TFs in gene induction and histone modification.

CONTACT

Institut für Pharmakologie und Toxikologie
Department für Biomedizinische Wissenschaften
Veterinärmedizinische Universität Wien

Veterinärplatz 1
A-1210 Vienna
Austria

veronika.sexl@vetmeduni.ac.at

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