THURSDAY, Feb. 21 (HealthDay News) -- A component of an important cell signaling pathway may be involved in the antioxidant response by controlling the expression of oxidative stress response genes together with another nuclear enzyme, according to research published in the Feb. 21 issue of Nature.
David L. Mellman, and colleagues from the University of Wisconsin-Madison, identified proteins that interacted with the nuclear type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKIα). PIPKIα generates phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2), a signaling molecule that regulates a number of cellular functions, the authors note.
The researchers found that PIPKIα was found in nuclear speckles and interacted with a poly(A) polymerase called speckle-targeted PIPKIα regulated-poly(A) polymerase (Star-PAP), whose activity was regulated by PtdIns4,5P2. The two enzymes controlled the expression of select messenger RNAs, including heme oxygenase-1 and other oxidative stress response genes, by regulating their 3'-end formation.
"Taken together, the data demonstrate a model by which phosphoinositide signaling works in tandem with complement pathways to regulate the activity of Star-PAP and the subsequent biosynthesis of its target mRNA," Mellman and colleagues conclude. "The results reveal a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression."
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