Abstract
Purpose :
The cAMP response element binding protein (CREB) is a general transcription factor whose functions are modulated by ATF4. In the present study using mouse model and cultured cells as model systems, we first examined the interactions between CREB and ATF4, and their regulation of apoptosis of lens epithelial cells through control of aB-crystallin gene and p53-mediated apoptotic pathway
Methods :
RNA-seq, qRT-PCR, Western blot analysis and immunocytochemistry were used to analyze expression patterns of the CREB downstream genes. Co-IP and immunocytochemistry were used to determine protein-protein interaction. Over-expressing and knock-down were used to analyze the effect of genes on lens differentiation.
Results :
CREB was highly expressed in the ocular lens from the very beginning (ED 10.5) to adult mouse eye lens. ATF modulates the function of CREB in regulating expression of different set of genes to control stress response and apoptosis.
Conclusions :
CREB is an important transcription factor for lens development, and its function is modulated by ATF4. (Supported by grants from National Natural Science Foundation of China, 81570824, 81770910, 81500738, 81500707, and 81700821 as well as the Fundamental Funds from the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.