Purchase this article with an account.
DW Li, Y Mao, H Xiang, J Wang; Human Bcl-2 Gene Regulates ERK/JNK MAP Kinases To Control Expression Of Crystallin Genes In Rabbit Lens Epithelial Cells, N/N1003A . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2352.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Bcl-2 is a well-established anti-apoptotic gene. Besides its anti-apoptotic role, Bcl-2 has other important functions. One of the functions, as we recently demonstrated (Mao et al., 2001, J. Biol Chem. 276, 43435-43445), is its regulation of expression of the gene encoding alphaB crystallin. To further explore the mechanism mediating this regulation, we have examined the Bcl-2 regulation of activities of ERK/JNK kinases as well as the effects of Bcl-2 on lens crystallin genes under inhibition of these MAP kinases. Methods: The total proteins and activity levels of ERK/p38/JNK kinases in vector and Bcl-2 stable expression clones were examined with Western blot analysis. Expression of the endogenous alphaB crystallin gene was examined with Western blot with or without the inhibition of ERK/p38/JNK. The CAT and luciferase reporter genes under control of either mouse alphaA, alphaB or betaA3/A1 promoters were introduced into either vector- or Bcl-2-transfected cells. The relative reporter gene expression levels were determined by CAT and luciferase assays. Results: Both ERK/JNK MAP kinases but not p38, are substantially activated in the Bcl-2 expression cells than vector-transfected cells. The observed down-regulation of endogenous alphaB crystallin gene in Bcl-2 expression cells is associated with activation of the ERK/JNK kinases. Inhibition of ERK/JNK MAP kinases in Bcl-2 expression cells restored the endogenous levels of alphaB-crystallin. The changed expression of the reporter crystallin genes in Bcl-2 expression cells also requires the modulated activity of ERK/JNK MAP kinases. Conclusions: Bcl-2 regulates activities of ERK/JNK MAP kinases to control expression of crystallin genes. Supported by NEI and NJ Foundation grants. None.
This PDF is available to Subscribers Only