Send to

Choose Destination
Nucleic Acids Res. 2011 Oct;39(18):7961-73. doi: 10.1093/nar/gkr549. Epub 2011 Jul 4.

CKI isoforms α and ε regulate Star-PAP target messages by controlling Star-PAP poly(A) polymerase activity and phosphoinositide stimulation.

Author information

Department of Pharmacology, University of Wisconsin-Madison, 1300 University Ave. University of Wisconsin Medical School, Madison, WI 53706, USA.


Star-PAP is a non-canonical, nuclear poly(A) polymerase (PAP) that is regulated by the lipid signaling molecule phosphatidylinositol 4,5 bisphosphate (PI4,5P(2)), and is required for the expression of a select set of mRNAs. It was previously reported that a PI4,5P(2) sensitive CKI isoform, CKIα associates with and phosphorylates Star-PAP in its catalytic domain. Here, we show that the oxidative stress-induced by tBHQ treatment stimulates the CKI mediated phosphorylation of Star-PAP, which is critical for both its polyadenylation activity and stimulation by PI4,5P(2). CKI activity was required for the expression and efficient 3'-end processing of its target mRNAs in vivo as well as the polyadenylation activity of Star-PAP in vitro. Specific CKI activity inhibitors (IC261 and CKI7) block in vivo Star-PAP activity, but the knockdown of CKIα did not equivalently inhibit the expression of Star-PAP targets. We show that in addition to CKIα, Star-PAP associates with another CKI isoform, CKIε in the Star-PAP complex that phosphorylates Star-PAP and complements the loss of CKIα. Knockdown of both CKI isoforms (α and ε) resulted in the loss of expression and the 3'-end processing of Star-PAP targets similar to the CKI activity inhibitors. Our results demonstrate that CKI isoforms α and ε modulate Star-PAP activity and regulates Star-PAP target messages.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center