Universität zu Köln

von Brandenstein, Melanie, Depping, Reinhard ORCID: 0000-0002-4860-6058, Schaefer, Ekaterine, Dienes, Hans-Peter and Fries, Jochen W. U. (2011). Protein kinase C alpha regulates nuclear pri-microRNA 15a release as part of endothelin signaling. Biochim. Biophys. Acta-Mol. Cell Res., 1813 (10). S. 1793 - 1803. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 0167-4889

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Abstract

Endothelin-1 induced signaling is characterized by an early induction of a nuclear factor-kappa B p65/mitogen-activated phosphokinase p38 transcription complex via its A-receptor versus a late induction via diacylglycerol, and protein kinase C. A possible interaction between these two pathways and a potential function for protein kinase C in this context has not previously been elucidated. Here we report that in Caki-1 tumor cells, protein kinase C alpha is a part of the transcription complex. With importin alpha 4 and alpha 5 as chaperones, the transcription complex transmigrates into the nucleus. Protein kinase C alpha blocks the nuclear release of primicroRNA 15a by direct binding shown by electrophoretic mobility shift assay and Duolink immune histology. The expression levels of miRNA 15a can be further manipulated by transfection of si-protein kinase C alpha, or an expression vector containing protein kinase C alpha or miRNA 15. The miRNA 15a regulation by protein kinase C alpha is detectable in different malignant human tumor cell lines (renal cell carcinoma, breast carcinoma, and melanoma). Furthermore, all three cell lines harbor both endothelin receptors (ETAR/ETBR). Specific blockage of each receptor leads to major reduction of miRNA 15a expression due to increased nuclear protein kinase C alpha translocation. We conclude that the nuclear binding of pri-microRNA 15a is a novel function of protein kinase C alpha, which plays an important role in endothelin-1 mediated signaling. Since several endothelin-sensitive, malignant tumor cell lines harbor this regulation, it could indicate a more general role in tumor biology. (C) 2011 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code von Brandenstein, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Depping, Reinhard UNSPECIFIED orcid.org/0000-0002-4860-6058 UNSPECIFIED Schaefer, Ekaterine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dienes, Hans-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Fries, Jochen W. U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488204
DOI:	10.1016/j.bbamcr.2011.06.006
Journal or Publication Title:	Biochim. Biophys. Acta-Mol. Cell Res.
Volume:	1813
Number:	10
Page Range:	S. 1793 - 1803
Date:	2011
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	0167-4889
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; P38 MAPK; CANCER; RECEPTORS; TRANSDUCTION; EXPRESSION; APOPTOSIS; PATHWAYS; CELLS; GENE Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48820