The p53 transcription factor is the most frequently mutated tumor suppressor gene in human cancer. In approximately 50% of human cancers p53 is mutated and in many of the remaining cases, the function of the retained wild type p53 protein is compromised. p53 knockout mice develop tumors with short latency and 100% penetrance. These observations demonstrate the critical role of p53 in tumor prevention.
The Hippo tumor suppressor pathway is emerging as an important regulator of cancer-related processes. At the core of the Hippo pathway are two kinases, LATS1 and LATS2, which negatively regulate the pathway effectors, YAP and TAZ. YAP and TAZ are transcriptional co-activators that have been shown to promote or inhibit oncogenic transformation, in different contexts.
Chromatin modifications play key roles in the regulation of gene expression. Cancer cells often display altered chromatin modification patterns, which may contribute to their cancerous features. Our lab is studying one such particular modification: monoubiquitylation of histone H2B (H2B-ub), which is primarily carried out by the E3 ubiquitin ligase RNF20.