Jagadeeshan, S and Krishnamoorthy , YR and Singhal, M and Subramanian, A and Mavuluri, J and Lakshmi, A and Roshini, A and Baskar, G and Ravi, M and Joseph, LD and Sadasivan, K and Krishnan, A and Nair, AS and Venkatraman, G and Rayala , SK (2015) Transcriptional regulation of fibronectin by p21-activated kinase-1 modulates pancreatic tumorigenesis. Oncogene, 34. pp. 455-464. ISSN 1476-5594

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Abstract

Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing.

Item Type:	Article
Uncontrolled Keywords:	Pak1; fibronectin; PDAC; NF-κB–p65; KRAS intact model
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	23 Dec 2016 04:48
Last Modified:	22 Apr 2019 08:41
URI:	http://rgcb.sciencecentral.in/id/eprint/55

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