Abstract
Purpose: :
The tumor suppressor, p53 plays an important role in the ocular lens. Numerous laboratories have shown that during lens development, p53-mediated apoptosis of lens epithelial cells not only contributes to the formation of the normal lens and also mediates lens pathology under various conditions. Whether p53 can regulate lens differentiation remains to be elucidated. In the present study, we present various evidence to show that p53 can regulate c-Maf to control lens differentiation.
Methods: :
Both wild type and mutant (p53-/-) mice were used for the exploration of the p53 functions in regulating lens differentiation. Immunocytochemistry were used to explore the lenticular expression level of c-Maf in the two types of mice during development. Electronic gel mobility shifting assay, and Western-blot analysis were utilized to show that p53 directly controls c-Maf. ChIP assay was used to demonstrate that p53 can bind to c-Maf promoter in vivo.
Results: :
During mouse lens development, expression of c-Maf is significantly down-regulated in p53(-/-) mouse. C-Maf promoter contains a conserved p53 binding site through which P53 directly binds to c-Maf promoter both in vivo and in vitro. Through c-Maf, p53 can regulate expression of crystallin genes.
Conclusions: :
p53 regulates c-Maf to control lens differentiation.
Keywords: differentiation • gene/expression • transcription factors