Tousled like kinase signaling in cancer

Division Of Basic Sciences - Nci

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Abstract

We found that TLK depletion caused replication stress and provoked innate immune responses through the production of extrachromosomal telomeric DNA fragments and activation of the cGAS-STING pathway. As this predicts that TLK depletion could enhance immunotherapy approaches in a similar manner as STING agonists, we are planning to carry out in vitro and in vivo experiments to test this hypothesis in cancer models. We will carry out BioID based proteomics to examine chromatin changes upon TLK depletion or inhibition, analyze the functional impact of newly identified proximal interactors on histone deposition, characterize the impact of TLK2 loss of function in neurodevelopment and examine the impact of TLK loss on cancer growth, metastasis and chemotherapy responses.