Research Projects

TIF1γ is a molecule that negatively regulates TGF-β signaling, blocking differentiation in hematopoiesis. Its E3 ubiquitin ligase activity has been explored in cancer, with TIF1γ exerting a tumor suppressor role by inhibiting proliferation, EMT, and invasion. Previous research has shown that TIF1γ positively regulates self-renewal of cancer stem cells (CsCs). A RING domain mutant lacking E3 ubiquitin ligase activity still regulates self-renewal in oral cancer cells, suggesting that this activity is independent of its E3 ubiquitin ligase activity. Recent reports suggest that TIF1γ might have a transcriptional regulatory role, regulating the transcriptional repression of certain developmental genes like PU.1 and TAL1. Additionally, TIF1γ regulates transcriptional upregulation of IL17 during thymocyte development. TIF1γ interacts with transcriptional regulators like TRRAP and H2A.Z, which are not its E3 ubiquitin ligase substrates. The researchers hypothesize that TIF1γ recruits TRRAP and H2A.Z to promoters of self-renewal genes in a complex with other transcription factors to regulate a unique transcription program leading to CsC self-renewal. The project aims to identify TIF1γ's E3-ubiquitin ligase-independent transcriptional program for self-renewal in cancer. If the self-renewal regulatory role of TIF1γ is E3 ligase independent, drug molecules could be designed that specifically target the E3-independent activity without altering its E3-ligase-dependent tumor suppressive role.