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Sudheesh, A.P. and Rakesh S. , Laishram (2018) Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion. Molecular and cellular biology, 38 (5). e00457-17. ISSN 1098-5549

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Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer.

Item Type: Article
Uncontrolled Keywords: 3′-end RNA processing, Star-PAP, PIPKIα, nuclear phosphoinositide signal, cell invasion, phosphorylation
Subjects: Cardiovascular Diseases And Diabetes Biology
Depositing User: Rgcb Library
Date Deposited: 27 Jun 2018 06:20
Last Modified: 27 Jun 2018 06:20
URI: http://rgcb.sciencecentral.in/id/eprint/622

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