Browsing by Subject "C-terminal binding protein"

Animals regulate their metabolism dynamically as a response to changes in nutritional landscape. Intestine is emerging as a key regulator of systemic metabolism. It possesses secretory enteroendocrine cells (EECs), which have a central role in intestinal nutrient sensing and signaling. However, how the number and function of EECs is regulated in response to nutrients remains poorly understood. Previous work in Hietakangas lab has shown that a transcriptional cofactor, C-terminal binding protein (CtBP), regulates the number of EECs in response to sugar feeding and loss of CtBP function in EECs causes sugar intolerance in Drosophila. CtBP’s transcriptional activity is modulated through homodimerization, which is controlled by redox coenzyme NAD+/NADH, whose levels are dependent on sugar metabolism. Therefore, I hypothesise that CtBP is a sugar- and redox-responsive regulator of EEC function. In this thesis, I aimed to understand how CtBP is regulated and what are its downstream effectors. My results show that the formation of CtBP homodimers is responsive to dietary sugars and cellular redox state. In addition, I observed that CtBP heterodimerizes with EEC fate determining transcription factor Prospero. Functional analysis of CtBP downstream effector genes shows significant overlap with those of Prospero. In conclusion, CtBP is a sugar- and redox-responsive cellular regulator of EEC function, which acts in cooperation with Prospero.